8FU4

HCMV US11 peptide binding to HLA-A*02:01

8FU4 の概要

• エントリーDOI: 10.2210/pdb8fu4/pdb
• 関連するPDBエントリー: 8FRT
• 分子名称: HLA-A*02:01 alpha chain, Beta-2-microglobulin, TLF: TLFDEPPPL, ... (7 entities in total)
• 機能のキーワード: immunoevasin, molecular mimicry, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 45208.49

構造登録者

Watson, G.M.,Berry, R.,Littler, D.R.,Rossjohn, J. (登録日: 2023-01-16, 公開日: 2024-03-27, 最終更新日: 2024-10-16)

主引用文献

Zimmermann, C.,Watson, G.M.,Bauersfeld, L.,Berry, R.,Ciblis, B.,Lan, H.,Gerke, C.,Oberhardt, V.,Fuchs, J.,Hofmann, M.,Freund, C.,Rossjohn, J.,Momburg, F.,Hengel, H.,Halenius, A.
Diverse cytomegalovirus US11 antagonism and MHC-A evasion strategies reveal a tit-for-tat coevolutionary arms race in hominids.
Proc.Natl.Acad.Sci.USA, 121:e2315985121-e2315985121, 2024

PubMed Abstract: Recurrent, ancient arms races between viruses and hosts have shaped both host immunological defense strategies as well as viral countermeasures. One such battle is waged by the glycoprotein US11 encoded by the persisting human cytomegalovirus. US11 mediates degradation of major histocompatibility class I (MHC-I) molecules to prevent CD8+ T-cell activation. Here, we studied the consequences of the arms race between US11 and primate MHC-A proteins, leading us to uncover a tit-for-tat coevolution and its impact on MHC-A diversification. We found that US11 spurred MHC-A adaptation to evade viral antagonism: In an ancestor of great apes, the MHC-A A2 lineage acquired a Pro184Ala mutation, which confers resistance against the ancestral US11 targeting strategy. In response, US11 deployed a unique low-complexity region (LCR), which exploits the MHC-I peptide loading complex to target the MHC-A2 peptide-binding groove. In addition, the global spread of the human HLA-A*02 allelic family prompted US11 to employ a superior LCR strategy with an optimally fitting peptide mimetic that specifically antagonizes HLA-A*02. Thus, despite cytomegaloviruses low pathogenic potential, the increasing commitment of US11 to MHC-A has significantly promoted diversification of MHC-A in hominids.

PubMed: 38377192
DOI: 10.1073/pnas.2315985121

実験手法

X-RAY DIFFRACTION (1.6 Å)