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Structure paper

タイトル	Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor.
ジャーナル・号・ページ	Nature, Vol. 598, Issue 7882, Page 672-676, Year 2021
掲載日	2021年10月13日
著者	Katherine Basore / Hongming Ma / Natasha M Kafai / Samantha Mackin / Arthur S Kim / Christopher A Nelson / Michael S Diamond / Daved H Fremont /
PubMed 要旨	LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV), a New World alphavirus that causes severe neurological disease in humans. Here we present ...LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV), a New World alphavirus that causes severe neurological disease in humans. Here we present near-atomic-resolution cryo-electron microscopy reconstructions of VEEV virus-like particles alone and in a complex with the ectodomains of LDLRAD3. Domain 1 of LDLRAD3 is a low-density lipoprotein receptor type-A module that binds to VEEV by wedging into a cleft created by two adjacent E2-E1 heterodimers in one trimeric spike, and engages domains A and B of E2 and the fusion loop in E1. Atomic modelling of this interface is supported by mutagenesis and anti-VEEV antibody binding competition assays. Notably, VEEV engages LDLRAD3 in a manner that is similar to the way that arthritogenic alphaviruses bind to the structurally unrelated MXRA8 receptor, but with a much smaller interface. These studies further elucidate the structural basis of alphavirus-receptor interactions, which could inform the development of therapies to mitigate infection and disease against multiple members of this family.
リンク	Nature / PubMed:34646020 / PubMed Central
手法	EM (単粒子)
解像度	4.2 - 4.97 Å
構造データ	24116 7n1h EMDB-24116, PDB-7n1h: CryoEM structure of Venezuelan equine encephalitis virus VLP in complex with the LDLRAD3 receptor 手法: EM (単粒子) / 解像度: 4.3 Å 24117 7n1i EMDB-24117, PDB-7n1i: CryoEM structure of Venezuelan equine encephalitis virus VLP 手法: EM (単粒子) / 解像度: 4.2 Å EMDB-24394: Unsharpened electron microscopy map of Venezuelan equine encephalitis VLP in complex with Domains 1 and 2 of LDLRAD3 receptor 手法: EM (単粒子) / 解像度: 4.97 Å
化合物	ChemComp-CA: Unknown entry / カルシウムジカチオン ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン
由来	venezuelan equine encephalitis virus (ベネズエラウマ脳炎ウイルス) mus musculus (ハツカネズミ)
キーワード	VIRUS LIKE PARTICLE (ウイルス様粒子) / VEEV / viral envelope (エンベロープ (ウイルス)) / host receptor / low-density lipoprotein receptor type-A module / LDLRAD3 / encephalitic alphavirus / Structural Genomics (構造ゲノミクス) / Center for Structural Genomics of Infectious Diseases / CSGID / VLP