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Structure paper

タイトル	Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor.
ジャーナル・号・ページ	Cell, Vol. 177, Issue 7, Page 1725-1737.e16, Year 2019
掲載日	2019年6月13日
著者	Katherine Basore / Arthur S Kim / Christopher A Nelson / Rong Zhang / Brittany K Smith / Carla Uranga / Lo Vang / Ming Cheng / Michael L Gross / Jonathan Smith / Michael S Diamond / Daved H Fremont /
PubMed 要旨	Mxra8 is a receptor for multiple arthritogenic alphaviruses that cause debilitating acute and chronic musculoskeletal disease in humans. Herein, we present a 2.2 Å resolution X-ray crystal ...Mxra8 is a receptor for multiple arthritogenic alphaviruses that cause debilitating acute and chronic musculoskeletal disease in humans. Herein, we present a 2.2 Å resolution X-ray crystal structure of Mxra8 and 4 to 5 Å resolution cryo-electron microscopy reconstructions of Mxra8 bound to chikungunya (CHIKV) virus-like particles and infectious virus. The Mxra8 ectodomain contains two strand-swapped Ig-like domains oriented in a unique disulfide-linked head-to-head arrangement. Mxra8 binds by wedging into a cleft created by two adjacent CHIKV E2-E1 heterodimers in one trimeric spike and engaging a neighboring spike. Two binding modes are observed with the fully mature VLP, with one Mxra8 binding with unique contacts. Only the high-affinity binding mode was observed in the complex with infectious CHIKV, as viral maturation and E3 occupancy appear to influence receptor binding-site usage. Our studies provide insight into how Mxra8 binds CHIKV and creates a path for developing alphavirus entry inhibitors.
リンク	Cell / PubMed:31080061 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	2.2 - 4.99 Å
構造データ	9393 6nk5 EMDB-9393, PDB-6nk5: Electron Cryo-Microscopy Of Chikungunya VLP 手法: EM (単粒子) / 解像度: 4.16 Å 9394 6nk6 EMDB-9394, PDB-6nk6: Electron Cryo-Microscopy Of Chikungunya VLP in complex with mouse Mxra8 receptor 手法: EM (単粒子) / 解像度: 4.06 Å 9395 6nk7 EMDB-9395, PDB-6nk7: Electron Cryo-Microscopy of Chikungunya in Complex with Mouse Mxra8 Receptor 手法: EM (単粒子) / 解像度: 4.99 Å PDB-6nk3: Crystal structure of murine Mxra8 ectodomain 手法: X-RAY DIFFRACTION / 解像度: 2.2 Å
化合物	ChemComp-HOH: WATER / 水 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	chikungunya virus (strain 37997) (チクングニア熱) mus musculus (ハツカネズミ) chikungunya virus strain senegal 37997 (チクングニア熱) chikungunya virus (チクングニヤウイルス)
キーワード	CELL INVASION / Chikungunya (チクングニア熱) / virus receptor / Immunoglobulin-like (抗体) / Structural Genomics (構造ゲノミクス) / Center for Structural Genomics of Infectious Diseases / CSGID / VIRUS LIKE PARTICLE (ウイルス様粒子) / virus-like particle (ウイルス様粒子) / VIRUS LIKE PARTICLE/SIGNALING PROTEIN / viral receptor / Mxra8 / VIRUS LIKE PARTICLE-SIGNALING PROTEIN complex / VIRUS (ウイルス)