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1.
Plast Reconstr Surg ; 2023 May 26.
Article in English | MEDLINE | ID: mdl-37252912

ABSTRACT

SUMMARY: A misshaped pinna, caused by extrinsic pressures such as birth canal extrusion or incorrect position, is typically one of congenital auricular deformities in newborns. As an approach to this deformity, surgery is a routine option, but it may lead to uncomfortable outcomes traumatically and aesthetically. Commercial ear mold orthosis with uniform size has achieved an effect of non-surgical orthotic treatment, but it is not applicable among all newborns in terms of the auricle morphologies. This research was to employ the CAD and 3D printing technology to develop a novel customized orthosis for congenital auricular deformities. The 3D models of the ears were reconstructed using CAD soft and a novel customized orthosis model was established after a process of correction, adjustment, and construction with simple wearing and precise matching to allow its tight attachment to the outer ear free from uneven skin pressing. After 3D printing customized orthosis injection mold, medical silicon injection molding was used to produce customized orthosis. Clinical application was conducted in three newborns and achieved satisfactory results. This novel customized auricle orthosis is expected to spread clinically for the purposes of improving the cure rate of non-surgical correction and reducing the occurrence of complications from surgery and anesthesia.

2.
J Environ Public Health ; 2022: 2068963, 2022.
Article in English | MEDLINE | ID: mdl-36254304

ABSTRACT

As China enters a new era, the role of consumption as a driving force for the economy has become increasingly prominent. The consumption of rural residents is not only a matter of high-quality economic development but also an important part of realizing people's aspirations for a better life. This study contributes to the literature by establishing an econometric model based on the construction of a theoretical model for optimizing the utility of household consumption, using panel data from China's 31 provinces, eliminating endogenesis by using instrumental variables, taking 2SLS and dynamic GMM. The results show that the relationship between income uncertainty and rural residents' consumption varies in the same direction, stimulating consumption when real income exceeds psychological income and reducing consumption when real income does not reach psychological income. The quantile model shows that income uncertainty has a greater impact on the middle-high-consumption groups and a smaller impact on the lower-income groups.


Subject(s)
Income , Rural Population , China , Humans , Uncertainty
3.
Biomedicines ; 10(9)2022 Sep 07.
Article in English | MEDLINE | ID: mdl-36140323

ABSTRACT

Various risk factors are associated with neonatal sepsis; however, its relationship to maternal postpartum fever is unknown. This study aimed to determine the relationship between maternal postpartum fever and neonatal sepsis. Full-term and late preterm stable infants born from January 2019 to June 2021 and whose mothers developed intra- or post-partum fever were included in the study. After the newborns were transferred to the nursery, laboratory assessments were performed. Based on clinical conditions and data, the newborns were divided into unlikely sepsis and probable/proven sepsis groups. Maternal fever onset, duration, and maximum body temperature were recorded. We included 1059 newborns whose mothers developed fever intra-partum (n = 192), post-partum (n = 844), and intra- and post-partum (n = 23). The newborns were grouped into those with unlikely sepsis (n = 550) and those with probable/proven sepsis (n = 509). The incidence of intrapartum fever was higher in the probable/proven sepsis group than in the unlikely sepsis group (27.9% vs. 13.3%, p < 0.001). The incidence of postpartum fever was lower in the probable/proven sepsis group than in the unlikely sepsis group (74.7% vs. 88.5%, p < 0.001). Development of maternal fever within 1.8 h postpartum and a newborn respiratory rate of >60 breaths/min were positive predictors (91.6%) for neonatal probable/proven sepsis.

4.
BMC Endocr Disord ; 22(1): 67, 2022 Mar 15.
Article in English | MEDLINE | ID: mdl-35291991

ABSTRACT

BACKGROUND: Circular RNA (circRNA) has been shown to mediate diabetic nephropathy (DN) development by regulating renal tubular epithelial cells (RTECs) injury. However, the role and mechanism of circ_0000064 in high glucose (HG)-induced RTECs injury have not been fully elucidated. METHODS: Human RTECs (HK-2) were exposed to HG to induce cell injury. Cell oxidative stress was assessed by detecting the levels of oxidative stress-markers. Moreover, cell proliferation and apoptosis were determined by CCK8 assay, EDU assay and flow cytometry. The protein levels of proliferation markers, apoptosis markers and Rho-associated coiled-coil-containing kinase 1 (ROCK1) were measured using western blot analysis. Furthermore, quantitative real-time PCR was performed to assess the expression of circ_0000064, microRNA (miR)-532-3p and ROCK1. The interaction between miR-532-3p and circ_0000064 or ROCK1 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. RESULTS: Our results revealed that HG treatment could promote HK-2 cells oxidative stress, apoptosis, fibrosis, and inhibit proliferation. Circ_0000064 expression was increased in the serum of DN patients and HG-induced HK-2 cells, and silenced circ_0000064 could relieve HG-induced HK-2 cells injury. MiR-532-3p could be sponged by circ_0000064, and its overexpression also alleviated HG-induced HK-2 cells injury. Besides, the regulation of circ_0000064 knockdown on HG-induced HK-2 cells injury could be reversed by miR-532-3p inhibitor. Additionally, ROCK1 was a target of miR-532-3p, and its expression was inhibited by circ_0000064 knockdown. The inhibition effect of circ_0000064 knockdown on HG-induced HK-2 cells injury also could be reversed by overexpressing ROCK1. CONCLUSION: In summary, circ_0000064 knockdown might alleviate HG-induced HK-2 cells injury via regulating the miR-532-3p/ROCK1 axis, which provided a new perspective for DN treatment.


Subject(s)
Diabetic Nephropathies/metabolism , Epithelial Cells/metabolism , Kidney Tubules/metabolism , MicroRNAs/metabolism , RNA, Circular/metabolism , rho-Associated Kinases/metabolism , Disease Progression , Glucose/pharmacology , Humans
6.
Org Biomol Chem ; 20(6): 1226-1230, 2022 02 09.
Article in English | MEDLINE | ID: mdl-35040852

ABSTRACT

Here, we report a metal-free approach for the construction of methylene-bridged bis-1,3-dicarbonyl compounds via cross-dehydrogenative coupling of 1,3-dicarbonyl compounds with 2-methoxyethanol. In addition, we have extended this methodology to synthesize tetra-substituted pyridine derivatives using 1,3-dicarbonyl, 2-methoxyethanol and NH4OAc in one step. The key advantages include accepting a wide range of substrates, utilizing O2 as the sole oxidant, and synthesizing biologically active compounds such as 1,4-dihydropyridine and pyrazole.

7.
Article in English | MEDLINE | ID: mdl-34518767

ABSTRACT

BACKGROUND: Hypertrophic scar (HS) is a benign fibroproliferative skin disease resulting from an aberrant wound healing process and can cause aesthetic and functional damage to patients. Currently, there is no ideal treatment to treat this disease. Galangin, a natural active bioflavonoid compound, is suggested to inhibit fibrosis and proliferation in certain cells. METHODS: In this study, we found Galangin could attenuate abnormal scar formation in an HS rabbit ear model. Additionally, the HE staining shows Galangin reduced scar elevation index (SEI) and Masson's trichrome staining changed collagen deposition. RESULTS: The expressions of type I collagen, type III collagen, and TGF-ß1 were much lower under a proper dose of Galangin treatment, and Smad7 expression was also enhanced, which are examined by real-time PCR, immunohistochemistry, and western blot. CONCLUSION: Our data indicated that Galangin can alleviate dermal scarring via the TGF-ß/Smad signaling pathway probably by upregulating Smad 7 expression and, thus, suppressing the expression of type I and type III collagens and TGF-ß1.

8.
Front Psychol ; 10: 801, 2019.
Article in English | MEDLINE | ID: mdl-31024413

ABSTRACT

Focusing on knowledge-based service relationships, this study examined knowledge-based service workers' (i.e., school teachers) emotional labor process and the consequential outcomes for their well-being. The study also examined the roles of two antecedents, namely, teachers' perceptions of display rules and self-monitoring tendencies. A sample of 1,656 school teachers participated in the study. The results showed that self-monitoring generally had stronger, though maladaptive, effects than display rule perceptions on individuals' use of emotional labor strategies (ELS) (i.e., surface acting and deep acting) and well-being (i.e., anxiety, depression, contentment, and enthusiasm). Both self-monitoring and display rule perceptions were positively related to two ELS. There were relatively stronger relationships between self-monitoring and surface acting, and between display rule perceptions and deep acting. Surface acting was positively related to anxiety and depression and negatively related to contentment and enthusiasm. Deep acting was positively related to anxiety, contentment, and enthusiasm. The examination of indirect effects showed that self-monitoring was positively related to anxiety and depression and negatively related to enthusiasm and contentment. Display rule perceptions were weakly, but positively, related to anxiety and depression. These results suggest that self-monitoring may be less beneficial than previously thought. Knowledge-based service workers' display rule perceptions and deep acting may not necessarily be harmful to their well-being, but reflect their role identification and commitment. Theoretical contributions and practical suggestions of this study were discussed.

9.
Front Psychol ; 10: 190, 2019.
Article in English | MEDLINE | ID: mdl-30792677

ABSTRACT

The emotional aspects of teaching are important and teachers' emotional labor, or, how teachers manage emotions at school, has been attracting more and more attention recently. Using multi-group structural equation modeling, this study investigated the measurement invariance of, and the relationships between, teachers' emotional labor strategies and teaching satisfaction. Participants included teachers from primary and secondary schools in Hong Kong and mainland China. Three sets of group comparisons have been made between female and male teachers, between primary and secondary school teachers, and between teachers in Hong Kong and mainland China. The multi-group invariance tests showed no significant subgroup differences in the measurement and structural models. Thus, there was no difference of 'kind.' However, some differences of 'degree' were observed across genders, grade levels and regions. These differences in the relationship between surface/deep acting and teaching satisfaction can be attributed to the possible influence of some cognitive factors and socio-cultural contexts. With due methodological rigor, the results of this study provide deeper understanding of teachers' emotional labor and its relationship with teaching satisfaction.

10.
Front Psychol ; 9: 2395, 2018.
Article in English | MEDLINE | ID: mdl-30555395

ABSTRACT

This study integrated personal factors into the job demands-resources (JD-R) model to examine school- and individual-level predictors of teacher well-being. Survey data were gathered from 1,656 teachers from 54 schools. The results of hierarchical linear modeling indicated that the school-level emotional job demands of teaching and suppression at the individual level were positively related to teachers' anxiety and depression whereas school-level trust in colleagues and individual-level reappraisal were positively associated with enthusiasm and contentment. Positive relationship between emotional job demands and suppression was also found. These findings support the claim that reappraisal should be considered a personal resource and suppression a personal demand.

11.
Article in English | MEDLINE | ID: mdl-27649216

ABSTRACT

Based on an adjusted Job Demands-Resources (JD-R) model that considers the mediation of personal resources, this study examined the relationships between two characteristics of teachers' work environment (i.e., emotional job demands and trust in colleagues) and two indicators of teachers' well-being (i.e., teaching satisfaction and emotional exhaustion). In particular, the study focused on how emotion regulation strategies (i.e., reappraisal and suppression) mediate these relationships. Data collected from a questionnaire survey of 1115 primary school teachers in Hong Kong was analyzed to test the hypothesized relationships. The results of structural equation modeling indicated that: (1) the emotional job demands of teaching were detrimental to teacher well-being, whereas trust in colleagues was beneficial; (2) both emotion regulation strategies mediated the relationships between both emotional job demands and trust in colleagues and teacher well-being; and (3) teachers who tend to use more reappraisal may be psychologically healthier than those tend to adopt more suppression. These findings support the applicability of the JD-R model to school settings and highlight the role of teachers' emotion regulation in teachers' well-being. Implications for the improvement of school environments and teachers' well-being are identified.


Subject(s)
Emotions , School Teachers/psychology , Workplace/psychology , Adult , Female , Hong Kong/epidemiology , Humans , Male , Middle Aged , Personal Satisfaction , Social Environment , Trust
12.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 40(2): 182-7, 2015 Feb.
Article in Chinese | MEDLINE | ID: mdl-25769332

ABSTRACT

OBJECTIVE: To observe the long-term efficacy of two double-head compression titanium screw anterior and posterior cross internal fixation on femoral neck fracture. METHODS: A total of 80 patients with the femoral neck fracture, from January 2010 to December 2013 in the Second Xiangya Hospital, Central South University, were selected and divided into an experimental group (n=50) and a control group (n=30). Th e experimental group received the treatment of two compression titanium screw anterior and posterior internal fixation, while the control group received three titanium screw internal fixation. Surgery time and intraoperative blood loss and postoperative Harris hip score were compared between the 2 groups. RESULTS: Th e operative time in the experimental group was (41.6±6.4) min, which was shorter than that in the control group [(50.1±7.2) min], the postoperative bleeding loss was (20.2±8.1) mL, which was less than that in the control group [(31.4±9.8) mL], with significant difference (both P<0.05). The excellence rate of Harris hip score was 94.0% in the experimental group, while that in the control group was 93.3%, with no significant difference (P>0.05). CONCLUSION: Two double-head compression titanium anterior and posterior cross internal fixation shows a good long-term efficacy on femoral neck fracture, which holds important clinical value and should be widely spread.


Subject(s)
Bone Screws , Femoral Neck Fractures , Fracture Fixation, Internal , Titanium , Blood Loss, Surgical , Humans , Postoperative Hemorrhage , Postoperative Period
13.
PLoS One ; 6(12): e28458, 2011.
Article in English | MEDLINE | ID: mdl-22162771

ABSTRACT

The ß-class carbonic anhydrases (ß-CAs) are widely distributed among lower eukaryotes, prokaryotes, archaea, and plants. Like all CAs, the ß-enzymes catalyze an important physiological reaction, namely the interconversion between carbon dioxide and bicarbonate. In plants the enzyme plays an important role in carbon fixation and metabolism. To further explore the structure-function relationship of ß-CA, we have determined the crystal structures of the photoautotroph unicellular green alga Coccomyxa ß-CA in complex with five different inhibitors: acetazolamide, thiocyanate, azide, iodide, and phosphate ions. The tetrameric Coccomyxa ß-CA structure is similar to other ß-CAs but it has a 15 amino acid extension in the C-terminal end, which stabilizes the tetramer by strengthening the interface. Four of the five inhibitors bind in a manner similar to what is found in complexes with α-type CAs. Iodide ions, however, make contact to the zinc ion via a zinc-bound water molecule or hydroxide ion--a type of binding mode not previously observed in any CA. Binding of inhibitors to Coccomyxa ß-CA is mediated by side-chain movements of the conserved residue Tyr-88, extending the width of the active site cavity with 1.5-1.8 Å. Structural analysis and comparisons with other α- and ß-class members suggest a catalytic mechanism in which the movements of Tyr-88 are important for the CO(2)-HCO(3)(-) interconversion, whereas a structurally conserved water molecule that bridges residues Tyr-88 and Gln-38, seems important for proton transfer, linking water molecules from the zinc-bound water to His-92 and buffer molecules.


Subject(s)
Acetazolamide/chemistry , Anions/chemistry , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrases/chemistry , Chlorophyta/metabolism , Buffers , Carbonic Anhydrase Inhibitors/pharmacology , Catalysis , Catalytic Domain , Crystallography, X-Ray/methods , Dimerization , Hydrogen Bonding , Hydrogen-Ion Concentration , Kinetics , Models, Molecular , Molecular Conformation , Protein Binding , Protein Conformation , Static Electricity , Tyrosine/chemistry
14.
Acta Crystallogr Sect F Struct Biol Cryst Commun ; 67(Pt 10): 1214-7, 2011 Oct 01.
Article in English | MEDLINE | ID: mdl-22102030

ABSTRACT

α-Actinins form antiparallel homodimers that are able to cross-link actin filaments. The protein contains three domains: an N-terminal actin-binding domain followed by a central rod domain and a calmodulin-like EF-hand domain at the C-terminus. Here, crystallization of the rod domain of Entamoeba histolytica α-actinin-2 is reported; it crystallized in space group P2(1)2(1)2(1), with unit-cell parameters a = 47.8, b = 79.1, c = 141.8 Å. A Matthews coefficient V(M) of 2.6 Å(3) Da(-1) suggests that there are two molecules and 52.5% solvent content in the asymmetric unit. A complete native data set extending to a d-spacing of 2.8 Å was collected on beamline I911-2 at MAX-lab, Sweden.


Subject(s)
Actinin/chemistry , Entamoeba histolytica/chemistry , Actinin/analysis , Crystallization , Crystallography, X-Ray
15.
Nat Struct Mol Biol ; 18(3): 389-91, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21336278

ABSTRACT

The signal recognition particle (SRP) recognizes and binds the signal sequence of nascent proteins as they emerge from the ribosome. We present here the 3.0-Å structure of a signal sequence bound to the Methanococcus jannaschii SRP core. Structural comparison with the free SRP core shows that signal-sequence binding induces formation of the GM-linker helix and a 180° flip of the NG domain-structural changes that ensure a hierarchical succession of events during protein targeting.


Subject(s)
Archaeal Proteins/chemistry , Archaeal Proteins/metabolism , Methanococcus/metabolism , Protein Sorting Signals , Signal Recognition Particle/chemistry , Signal Recognition Particle/metabolism , Base Sequence , Crystallography, X-Ray , Methanococcus/chemistry , Models, Molecular , Molecular Sequence Data , Protein Binding
16.
FEBS J ; 277(16): 3368-81, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20646069

ABSTRACT

In uropathogenic Escherichia coli, UPEC, different types of fimbriae are expressed to mediate interactions with host tissue. FocB belongs to the PapB family of transcription factors involved in the regulation of fimbriae gene clusters. Recent findings suggest that members from this family of proteins may form homomeric or heteromeric complexes and exert both positive and negative effects on the transcription of fimbriae genes. To elucidate the detailed function of FocB, we have determined its crystal structure at 1.4 A resolution. FocB is an all alpha-helical protein with a helix-turn-helix motif. Interestingly, conserved residues important for DNA-binding are located not in the postulated recognition helix of the motif, but in the preceding helix. Results from protein-DNA-binding studies suggest that FocB interacts with the minor groove of its cognate DNA target, which is indicative of a DNA interaction that is unusual for this motif. FocB crystallizes in the form of dimers. Packing interactions in the crystals give two plausible dimerization interfaces. Conserved residues, known to be important for protein oligomerization, are present at both interfaces, suggesting that both sites could play a role in a functional FocB protein.


Subject(s)
Adhesins, Bacterial/metabolism , DNA-Binding Proteins/chemistry , Escherichia coli Proteins/chemistry , Gene Expression Regulation, Bacterial , Models, Molecular , Uropathogenic Escherichia coli , Adhesins, Bacterial/genetics , Amino Acid Motifs , Amino Acid Sequence , Crystallography, X-Ray , DNA, Bacterial/metabolism , DNA-Binding Proteins/genetics , Dimerization , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , Membrane Proteins/metabolism , Molecular Sequence Data , Protein Structure, Tertiary , Sequence Alignment , Transcription Factors/metabolism
17.
Article in English | MEDLINE | ID: mdl-20208176

ABSTRACT

The transcription factor FocB belongs to a family of regulators encoded by several different fimbriae gene clusters in uropathogenic Escherichia coli. Recent findings suggest that FocB-family proteins may form different protein-protein complexes and that they may exert both positive and negative effects on the transcription of fimbriae genes. However, little is known about the actual role and mode of action when these proteins interact with the fimbriae operons. The 109-amino-acid FocB transcription factor from the foc gene cluster in E. coli strain J96 has been cloned, expressed and purified. The His(6)-tagged fusion protein was captured by Ni(2+)-affinity chromatography, cleaved with tobacco etch virus protease and purified by gel filtration. The purified protein is oligomeric, most likely in the form of dimers. NMR analysis guided the crystallization attempts by showing that probable conformational exchange or oligomerization is reduced at temperatures above 293 K and that removal of the highly flexible His(6) tag is advantageous. The protein was crystallized using the hanging-drop vapour-diffusion method at 295 K. A native data set to 2.0 A resolution was collected at 100 K using synchrotron radiation.


Subject(s)
DNA-Binding Proteins/chemistry , Escherichia coli Proteins/chemistry , Escherichia coli/chemistry , Adhesins, Escherichia coli/metabolism , Amino Acid Sequence , Chromatography, Gel , Circular Dichroism , Crystallization , Crystallography, X-Ray , DNA-Binding Proteins/isolation & purification , DNA-Binding Proteins/metabolism , Escherichia coli/metabolism , Escherichia coli Proteins/isolation & purification , Escherichia coli Proteins/metabolism , Molecular Sequence Data , Nuclear Magnetic Resonance, Biomolecular , Protein Binding , Temperature
18.
Proc Natl Acad Sci U S A ; 104(38): 14911-6, 2007 Sep 18.
Article in English | MEDLINE | ID: mdl-17846429

ABSTRACT

The signal-recognition particle (SRP) is a ubiquitous protein-RNA complex that targets proteins to cellular membranes for insertion or secretion. A key player in SRP-mediated protein targeting is the evolutionarily conserved core consisting of the SRP RNA and the multidomain protein SRP54. Communication between the SRP54 domains is critical for SRP function, where signal sequence binding at the M domain directs receptor binding at the GTPase domain (NG domain). These SRP activities are linked to domain rearrangements, for which the role of SRP RNA is not clear. In free SRP, a direct interaction of the GTPase domain with SRP RNA has been proposed but has never been structurally verified. In this study, we present the crystal structure at 2.5-A resolution of the SRP54-SRP19-SRP RNA complex of Methanococcus jannaschii SRP. The structure reveals an RNA-bound conformation of the SRP54 GTPase domain, in which the domain is spatially well separated from the signal peptide binding site. The association of both the N and G domains with SRP RNA in free SRP provides further structural evidence for the pivotal role of SRP RNA in the regulation of the SRP54 activity.


Subject(s)
Archaeal Proteins/chemistry , GTP Phosphohydrolases/chemistry , RNA, Small Cytoplasmic/chemistry , Signal Recognition Particle/chemistry , Archaeal Proteins/metabolism , Base Sequence , Binding Sites , Crystallography, X-Ray , GTP Phosphohydrolases/metabolism , Methanococcus/chemistry , Methanococcus/metabolism , Models, Molecular , Molecular Sequence Data , Nucleic Acid Conformation , Protein Structure, Tertiary , RNA, Small Cytoplasmic/metabolism , Signal Recognition Particle/metabolism , Structure-Activity Relationship
19.
RNA ; 11(7): 1043-50, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15928341

ABSTRACT

Proper assembly of large protein-RNA complexes requires sequential binding of the proteins to the RNA. The signal recognition particle (SRP) is a multiprotein-RNA complex responsible for the cotranslational targeting of proteins to biological membranes. Here we describe the crystal structure at 2.6-A resolution of the S-domain of SRP RNA from the archeon Methanococcus jannaschii. Comparison of this structure with the SRP19-bound form reveals the nature of the SRP19-induced conformational changes, which promote subsequent SRP54 attachment. These structural changes are initiated at the SRP19 binding site and transmitted through helix 6 to looped-out adenosines, which form tertiary RNA interaction with helix 8. Displacement of these adenosines enforces a conformational change of the asymmetric loop structure in helix 8. In free RNA, the three unpaired bases A195, C196, and C197 are directed toward the helical axis, whereas upon SRP19 binding the loop backbone inverts and the bases are splayed out in a conformation that resembles the SRP54-bound form. Nucleotides adjacent to the bulged nucleotides seem to be particularly important in the regulation of this loop transition. Binding of SRP19 to 7S RNA reveals an elegant mechanism of how protein-induced changes are directed through an RNA molecule and may relate to those regulating the assembly of other RNPs.


Subject(s)
Methanococcus/chemistry , RNA, Archaeal/chemistry , RNA, Archaeal/metabolism , Signal Recognition Particle/chemistry , Signal Recognition Particle/metabolism , Adenosine/chemistry , Base Sequence , Binding Sites , Chromatography, Gel , Crystallography, X-Ray , Cytosine/chemistry , Electrophoretic Mobility Shift Assay , Lactococcus lactis/genetics , Methanococcus/genetics , Models, Biological , Models, Molecular , Molecular Sequence Data , Nucleic Acid Conformation , Protein Binding , Protein Structure, Secondary , Protein Structure, Tertiary , RNA, Archaeal/genetics
20.
J Biol Chem ; 279(25): 26411-6, 2004 Jun 18.
Article in English | MEDLINE | ID: mdl-15082720

ABSTRACT

Transthyretin (TTR) is an extracellular transport protein involved in the distribution of thyroid hormones and vitamin A. So far, TTR has only been found in vertebrates, of which piscine TTR displays the lowest sequence identity with human TTR (47%). Human and piscine TTR bind both thyroid hormones 3,5,3'-triiodo-l-thyronine (T(3)) and 3,5,3',5'-tetraiodo-l-thyronine (thyroxine, T(4)). Human TTR has higher affinity for T(4) than T(3), whereas the reverse holds for piscine TTR. X-ray structures of Sparus aurata (sea bream) TTR have been determined as the apo-protein at 1.75 A resolution and bound to ligands T(3) and T(4), both at 1.9 A resolution. The apo structure is similar to human TTR with structural changes only at beta-strand D. This strand forms an extended loop conformation similar to the one in chicken TTR. The piscine TTR.T(4) complex shows the T(4)-binding site to be similar but not identical to human TTR, whereas the TTR.T(3) complex shows the I3' halogen situated at the site normally occupied by the hydroxyl group of T(4). The significantly wider entrance of the hormone-binding channel in sea bream TTR, in combination with its narrower cavity, provides a structural explanation for the different binding affinities of human and piscine TTR to T(3) and T(4).


Subject(s)
Prealbumin/chemistry , Thyroxine/chemistry , Triiodothyronine/chemistry , Animals , Chickens , Cloning, Molecular , Crystallography, X-Ray , Escherichia coli/metabolism , Humans , Ligands , Models, Molecular , Prealbumin/metabolism , Protein Binding , Protein Conformation , Protein Structure, Tertiary , Sea Bream
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