Peptidomes and Structures Illustrate Two Distinguishing Mechanisms of Alternating the Peptide Plasticity Caused by Swine MHC Class I Micropolymorphism.
Peptidomes and Structures Illustrate Two Distinguishing Mechanisms of Alternating the Peptide Plasticity Caused by Swine MHC Class I Micropolymorphism.
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肽体和结构说明了猪MHC I类微多态性引起肽可塑性交替的两种不同机制。
DOI：
10.3389/fimmu.2021.592447
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zhang N
中科院分区：
文献类型：
--
作者：
Wei X;Wang S;Li Z;Li Z;Qu Z;Wang S;Zou B;Liang R;Xia C;Zhang N
主要组织相容性复合物I类（MHC-I）的微多态性可以极大地改变肽呈递的可塑性，但阐明其潜在的机制仍然是一个挑战。在这里，我们研究了微多态性对猪MHC-I（称为猪白细胞抗原I类，SLA-I）分子的肽呈递的影响，通过我们新开发的随机肽库结合质谱（MS）从头测序方法（称为RPLD-MS）和相应的晶体结构确定的免疫肽。SLA-1*04：01、SLA-1*13：01及其突变体的免疫肽组显示，第156和99位残基的突变分别扩大和缩小了SLA-1分子所提呈的肽段范围。SLA-1*04：01的R156 A突变改变了口袋D的电荷性质，增大了口袋D的体积，消除了容纳肽的第三个（P3）锚残基的苛刻限制，扩大了肽的结合范围。与SLA-1*0401的99 Tyr相比，SLA-1*13：01的99 Phe不能与P3残基的骨架形成保守的氢键，导致口袋性质的变化较小，但免疫肽组的数量显著减少。P1-E和170 Arg形成的盐桥可以补偿这种力的缺失。这些数据说明了两种不同的方式，显示了微多态性如何改变SLA-I等位基因的肽结合可塑性，验证了RPLD-MS方法的灵敏度和准确性，用于确定肽结合特性的MHC-I在体外，并帮助更准确地预测和识别MHC-I限制性表位。
The micropolymorphism of major histocompatibility complex class I (MHC-I) can greatly alter the plasticity of peptide presentation, but elucidating the underlying mechanism remains a challenge. Here we investigated the impact of the micropolymorphism on peptide presentation of swine MHC-I (termed swine leukocyte antigen class I, SLA-I) molecules via immunopeptidomes that were determined by our newly developed random peptide library combined with the mass spectrometry (MS) de novo sequencing method (termed RPLD–MS) and the corresponding crystal structures. The immunopeptidomes of SLA-1*04:01, SLA-1*13:01, and their mutants showed that mutations of residues 156 and 99 could expand and narrow the ranges of peptides presented by SLA-I molecules, respectively. R156A mutation of SLA-1*04:01 altered the charge properties and enlarged the volume size of pocket D, which eliminated the harsh restriction to accommodate the third (P3) anchor residue of the peptide and expanded the peptide binding scope. Compared with 99Tyr of SLA-1*0401, 99Phe of SLA-1*13:01 could not form a conservative hydrogen bond with the backbone of the P3 residues, leading to fewer changes in the pocket properties but a significant decrease in quantitative of immunopeptidomes. This absent force could be compensated by the salt bridge formed by P1-E and 170Arg. These data illustrate two distinguishing manners that show how micropolymorphism alters the peptide-binding plasticity of SLA-I alleles, verifying the sensitivity and accuracy of the RPLD-MS method for determining the peptide binding characteristics of MHC-I in vitro and helping to more accurately predict and identify MHC-I restricted epitopes.
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影响因子：
32.4
作者：
Abelin JG;Keskin DB;Sarkizova S;Hartigan CR;Zhang W;Sidney J;Stevens J;Lane W;Zhang GL;Eisenhaure TM;Clauser KR;Hacohen N;Rooney MS;Carr SA;Wu CJ
通讯作者：
Wu CJ
影响因子：
3.3
作者：
Kløverpris HN;Cole DK;Fuller A;Carlson J;Beck K;Schauenburg AJ;Rizkallah PJ;Buus S;Sewell AK;Goulder P
通讯作者：
Goulder P
影响因子：
3.6
作者：
Fan, Shuhua;Wang, Yongli;Xia, Chun
通讯作者：
Xia, Chun
猪主要组织相容性复合物I类复合物的结构和生化分析及重要甲型流感病毒株表位图的预测
影响因子：
5.4
作者：
Fan, Shuhua;Wu, Yanan;Xia, Chun
通讯作者：
Xia, Chun
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH