Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing.
Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing.
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DOI：
10.1038/s41467-023-40736-6
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发表时间：
2023-08-18
影响因子：
16.6
通讯作者：
Bouvier, Marlene
中科院分区：
文献类型：
--
作者：
Li, Lenong;Peng, Xubiao;Batliwala, Mansoor;Bouvier, Marlene
研究表明，MHC I类（MHC I）分子在许多构象状态之间快速波动，这些运动支持肽采样。迄今为止，MHC I中间体在很大程度上未经实验表征，并且仍然难以捉摸。在这里，我们提出的X射线晶体结构的HLA-B8加载20聚体肽，显示出显着的扭曲在N-末端的沟。在电子密度图中缺失了长的N-末端氨基酸残基，形成了一个开放的凹槽。我们的结构还揭示了在沟的N-末端的MHC I-肽相互作用中非常不寻常的特征。分子动力学模拟表明，配合物具有不同程度的构象灵活性的方式与结构一致。我们认为，我们的结构已经捕获了显着的分子动力学的MHC I肽相互作用。在MHC I中肽依赖性构象运动的可视化是我们对高亲和力肽选择动力学概念理解的重要一步。MHC I-肽复合物的不寻常的晶体结构提供了凹槽在构象上适应结合肽的显着能力的可视化，解释了MHC I分子如何在抗原呈递中编辑肽。
Studies have suggested that MHC class I (MHC I) molecules fluctuate rapidly between numerous conformational states and these motions support peptide sampling. To date, MHC I intermediates are largely uncharacterized experimentally and remain elusive. Here, we present x-ray crystal structures of HLA-B8 loaded with 20mer peptides that show pronounced distortions at the N-terminus of the groove. Long stretches of N-terminal amino acid residues are missing in the electron density maps creating an open-ended groove. Our structures also reveal highly unusual features in MHC I-peptide interaction at the N-terminus of the groove. Molecular dynamics simulations indicate that the complexes have varying degrees of conformational flexibility in a manner consistent with the structures. We suggest that our structures have captured the remarkable molecular dynamics of MHC I-peptide interaction. The visualization of peptide-dependent conformational motions in MHC I is a major step forward in our conceptual understanding of dynamics in high-affinity peptide selection. The unusual crystal structures of MHC I-peptide complexes provide a visualization of the remarkable ability of the groove to adapt conformationally to bound peptides, explaining how MHC I molecules edit peptides in antigen presentation.
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影响因子：
11.4
作者：
Chen, Mingnan;Bouvier, Marlene
通讯作者：
Bouvier, Marlene
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
7.7
作者：
Hermann, Clemens;van Hateren, Andy;Boyle, Louise H.
通讯作者：
Boyle, Louise H.
影响因子：
4.8
作者：
Hawse, William F.;Gloor, Brian E.;Baker, Brian M.
通讯作者：
Baker, Brian M.
影响因子：
64.8
作者：
FALK, K;ROTZSCHKE, O;RAMMENSEE, HG
通讯作者：
RAMMENSEE, HG