Crystal structure of protein tyrosine phosphatase-2 from Cydia pomonella granulovirus.

Many viral genomes encode kinase and phosphatase enzymes to manipulate pathways that are controlled by phosphorylation events. The majority of viral phosphatase genes occur in the Baculoviridae and Poxviridae families of large DNA viruses. The corresponding protein sequences belong to four major homology groups, and structures are currently available for only two of these. Here, the first structure from the third group, the protein tyrosine phosphatase-2 (PTP-2) class of viral phosphatases, is described. It is shown that Cydia pomonella granulovirus PTP-2 has the same general fold and active-site architecture as described previously for other phosphatases, in the absence of significant sequence homology. Additionally, it has a novel C-terminal extension in an area corresponding to the interface of dimeric poxvirus phosphatases belonging to the Tyr-Ser protein phosphatase homology group.

Poly(L-lactide) nanocomposites containing poly(D-lactide) grafted nanohydroxyapatite with improved interfacial adhesion via stereocomplexation.

Biodegradable organic-inorganic composites composed of polylactide (PLA) and hydroxyapatite (HA) are important bone repairing materials, while the dispersibility of nanoscaled HA in PLA and the interfacial adhesion between HA and PLA remained unsatisfactory. In this study, poly(D-lactide) (PDLA) oligomers with different molecular weights were grafted onto HA nanorods (HA-PDLA), and the HA-PDLA hybrids were mixed with poly(L-lactide) (PLLA). Dispersibility of HA-PDLA hybrids in PLLA matrix was investigated, and the formation of PDLA/PLLA stereocomplex at the interface of HA-PDLA and PLLA was studied by characterizations including crystallization, mechanical and thermal properties, taking PLLA grafted HA (HA-PLLA) and unmodified HA as comparisons. Surface grafting of PLLA or PDLA oligomers both significantly improved the dispersibility of HA nanorods in PLLA matrix. Benefiting from PDLA/PLLA stereocomplexation, HA-PDLA could increase the tensile strength and the elongation of resulting PLLA/HA nanocomposites more significantly than HA-PLLA. The interfacial interaction between HA-PDLA and PLLA matrix could be further strengthened by increasing the molecular weights of those grafted PDLA chains on HA, which was verified by changes in crystallization and glass transition behaviors. To sum up, the concept of using PDLA/PLLA stereocomplexation was feasible and effective in preparing PLA-based organic-inorganic nanocomposites targeting bone repairing.

Structures of phlebovirus glycoprotein Gn and identification of a neutralizing antibody epitope.

Severe fever with thrombocytopenia syndrome virus (SFTSV) and Rift Valley fever virus (RVFV) are two arthropod-borne phleboviruses in the Bunyaviridae family, which cause severe illness in humans and animals. Glycoprotein N (Gn) is one of the envelope proteins on the virus surface and is a major antigenic component. Despite its importance for virus entry and fusion, the molecular features of the phleboviruse Gn were unknown. Here, we present the crystal structures of the Gn head domain from both SFTSV and RVFV, which display a similar compact triangular shape overall, while the three subdomains (domains I, II, and III) making up the Gn head display different arrangements. Ten cysteines in the Gn stem region are conserved among phleboviruses, four of which are responsible for Gn dimerization, as revealed in this study, and they are highly conserved for all members in Bunyaviridae Therefore, we propose an anchoring mode on the viral surface. The complex structure of the SFTSV Gn head and human neutralizing antibody MAb 4-5 reveals that helices α6 in subdomain III is the key component for neutralization. Importantly, the structure indicates that domain III is an ideal region recognized by specific neutralizing antibodies, while domain II is probably recognized by broadly neutralizing antibodies. Collectively, Gn is a desirable vaccine target, and our data provide a molecular basis for the rational design of vaccines against the diseases caused by phleboviruses and a model for bunyavirus Gn embedding on the viral surface.

XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma susceptibility: A meta-analysis of 11 case-control studies in an Asian population.

This meta-analysis was performed to evaluate the association between xeroderma pigmentosum complementary group D (XPD) Lys751Gln and Asp312Asn polymorphisms and susceptibility to hepatocellular carcinoma (HCC). PubMed, Embase, Google Scholar and the Chinese National Knowledge Infrastructure and the Chinese Biomedicine databases were systematically searched to identify relevant studies published up to June 1, 2014. Statistical analyses were performed using Stata version 12.0 software. A total of 11 case-control studies, comprising 2,852 cases and 2,936 controls, were included. The results of the meta-analysis revealed that a significant association between the risk of HCC and variant genotypes of the XPD Lys751Gln and Asp312Asn polymorphisms was evident in the homozygote comparison [Gln/Gln versus Lys/Lys: Odds ratio (OR), 1.831; 95% confidence interval (CI), 1.001-3.349], heterozygote comparison (Lys/Gln versus Lys/Lys: OR, 1.486; 95% CI, 1.044-2.114), dominant model (Gln/Gln + Lys/Gln versus Lys/Lys: OR, 1.540; 95% CI, 1.054-2.249) and allelic contrast (Gln-allele versus Lys-allele: OR, 1.453; 95% CI, 1.032-2.046) for the Lys751Gln polymorphism and the homozygote comparison for the Asp312Asn polymorphism (Asn/Asn versus Asp/Asp: OR, 1.352; 95% CI, 1.010-1.808). By contrast, no significant association was observed in the recessive model for the Lys751Gln polymorphism (Gln/Gln versus Lys/Gln + Lys/Lys: OR, 1.603; 95% CI, 0.924-2.779), or for the heterozygote comparison (Asn/Asp versus Asp/Asp: OR, 1.229; 95% CI, 0.857-1.762), dominant model (Asn/Asn + Asp/Asn versus Asp/Asp: OR, 1.249; 95% CI, 0.910-1.715), recessive model (Asn/Asn versus Asp/Asn + Asp/Asp: OR, 1.250; 95% CI, 0.940-1.663) or allelic contrast (Asn-allele versus Asp-allele: OR, 1.226; 95% CI, 0.965-1.557) for the Asp312Asn polymorphism. The present meta-analysis has indicated that the XPD Lys751Gln polymorphism could be a potential biomarker of HCC susceptibility and that the XPD Lys751Gln and Asp312Asn polymorphisms could be risk factors for HCC susceptibility in an Asian population; however, further large-scale and well-designed studies are required to reach a more precise and comprehensive conclusion.