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1.
Preprint in English | bioRxiv | ID: ppbiorxiv-177097

ABSTRACT

The recent outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid international spread pose a global health emergency. The trimeric spike (S) glycoprotein interacts with its receptor human ACE2 to mediate viral entry into host-cells. Here we present cryo-EM structures of an uncharacterized tightly closed SARS-CoV-2 S-trimer and the ACE2-bound-S-trimer at 2.7-Å and 3.8-Å-resolution, respectively. The tightly closed S-trimer with inactivated fusion peptide may represent the ground prefusion state. ACE2 binding to the up receptor-binding domain (RBD) within S-trimer triggers continuous swing-motions of ACE2-RBD, resulting in conformational dynamics of S1 subunits. Noteworthy, SARS-CoV-2 S-trimer appears much more sensitive to ACE2-receptor than SARS-CoV S-trimer in terms of receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and residue Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2, and provided structural basis of the spike D614G-mutation induced enhanced infectivity. Our findings offer a thorough picture on the mechanism of ACE2-induced conformational transitions of S-trimer from ground prefusion state towards postfusion state, thereby providing important information for development of vaccines and therapeutics aimed to block receptor binding.Competing Interest StatementThe authors have declared no competing interest.View Full Text

2.
Chinese Journal of Endemiology ; (12): 1003-1005, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-824098

ABSTRACT

Objective To study the urinary iodine level of pregnant women with thyroid disease in Shenzhen, and to provide scientific basis for rational iodine supplementation. Methods A total of 170 pregnant women with thyroid diseases who visited Department of Endocrinology, Peking University Shenzhen Hospital from January 2017 to March 2019 were selected as the subjects, they were divided into hyperthyroidism group (84 cases) and non-hyperthyroidism group (86 cases) according to whether they had hyperthyroidism or not. Morning urine sample was collected under normal dietary conditions; urinary iodine was detected by peroxyacetic acid tetramethylbenzidine oxidation colorimetry. Urinary iodine < 150 μg/L was iodine deficiency and 150 - 249 μg/L was appropriate iodine. Results The median of urinary iodine of pregnant women with thyroid disease in Shenzhen was 143.9 μg/L, which was slightly lower than the lowest limit of the appropriate iodine level. The median of urinary iodine in hyperthyroidism group was 116.6 μg/L, which was at the iodine deficiency level; the median of urinary iodine in non -hyperthyroidism group was 181.6 μg/L , which was at the appropriate iodine level. There was significant difference in urinary iodine levels between hyperthyroidism group and non-hyperthyroidism group (Z =- 2.261, P < 0.05). Conclusion The urinary iodine of pregnant women with hyperthyroidism in Shenzhen is slightly low.

3.
Chinese Journal of Endemiology ; (12): 1003-1005, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-800071

ABSTRACT

Objective@#To study the urinary iodine level of pregnant women with thyroid disease in Shenzhen, and to provide scientific basis for rational iodine supplementation.@*Methods@#A total of 170 pregnant women with thyroid diseases who visited Department of Endocrinology, Peking University Shenzhen Hospital from January 2017 to March 2019 were selected as the subjects, they were divided into hyperthyroidism group (84 cases) and non-hyperthyroidism group (86 cases) according to whether they had hyperthyroidism or not. Morning urine sample was collected under normal dietary conditions; urinary iodine was detected by peroxyacetic acid tetramethylbenzidine oxidation colorimetry. Urinary iodine < 150 μg/L was iodine deficiency and 150-249 μg/L was appropriate iodine.@*Results@#The median of urinary iodine of pregnant women with thyroid disease in Shenzhen was 143.9 μg/L, which was slightly lower than the lowest limit of the appropriate iodine level. The median of urinary iodine in hyperthyroidism group was 116.6 μg/L, which was at the iodine deficiency level; the median of urinary iodine in non-hyperthyroidism group was 181.6 μg/L, which was at the appropriate iodine level. There was significant difference in urinary iodine levels between hyperthyroidism group and non-hyperthyroidism group (Z =-2.261, P < 0.05).@*Conclusion@#The urinary iodine of pregnant women with hyperthyroidism in Shenzhen is slightly low.

4.
Chinese Journal of Biotechnology ; (12): 683-691, 2017.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-310623

ABSTRACT

Adaboost algorithm with improved K-nearest neighbor classifiers is proposed to predict protein subcellular locations. Improved K-nearest neighbor classifier uses three sequence feature vectors including amino acid composition, dipeptide and pseudo amino acid composition of protein sequence. K-nearest neighbor uses Blast in classification stage. The overall success rates by the jackknife test on two data sets of CH317 and Gram1253 are 92.4% and 93.1%. Adaboost algorithm with the novel K-nearest neighbor improved by Blast is an effective method for predicting subcellular locations of proteins.

5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-487926

ABSTRACT

By using the high resolution mass spectrometer TripleTOF 5600 , three kinds of standard proteins including bovine serum albumin ( BSA) , ovalbumin ( OVA) and lysozyme C( LYZC) were analyzed, and the correlationship between the ion intensity of mass spectrometry and the relative content of protein sample was investigated. The protein samples were digested by trypsion and diluted to 1-1024 fmol in 7 μL. The ion counts per second ( cps) were used to stand for the amounts of proteins and peptides. Then the correlation between sum of ion intensity ( cps) of all the peptides, number of peptides detected and the amount of proteins was investigated. By comparing the change of values of the same sample in three parallel experiments, a linear relationship between these indexes and the amount of proteins within 1-1024 fmol was found when the cps was more than 1000. Usually, the maximal ion intensity was no more than 1. 5 times of the minimum value for same peptide in triplicate experiments, which suggested that the 3 times or more change of ion intensity was the minimum threshold to determine the differences of proteins amounts in different samples. This study provides a relative quantitative analysis method using qualitative data of high resolution and high scan speed mass spectrometry, which can quickly and easily provide reference for biological and medical research.

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