6ORT

Crystal Structure of Bos taurus Mxra8 Ectodomain

6ORT の概要

• エントリーDOI: 10.2210/pdb6ort/pdb
• 分子名称: Matrix remodeling-associated protein 8, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: receptor, chikungunya virus, cow, bovine, alphavirus, moo insertion, structural genomics, center for structural genomics of infectious diseases, csgid, membrane protein
• 由来する生物種: Bos taurus (Bovine)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32711.65

構造登録者

Fremont, D.H.,Kim, A.S.,Nelson, C.A.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2019-04-30, 公開日: 2020-03-04, 最終更新日: 2024-10-16)

主引用文献

Kim, A.S.,Zimmerman, O.,Fox, J.M.,Nelson, C.A.,Basore, K.,Zhang, R.,Durnell, L.,Desai, C.,Bullock, C.,Deem, S.L.,Oppenheimer, J.,Shapiro, B.,Wang, T.,Cherry, S.,Coyne, C.B.,Handley, S.A.,Landis, M.J.,Fremont, D.H.,Diamond, M.S.
An Evolutionary Insertion in the Mxra8 Receptor-Binding Site Confers Resistance to Alphavirus Infection and Pathogenesis.
Cell Host Microbe, 27:428-440.e9, 2020

PubMed Abstract: Alphaviruses are emerging, mosquito-transmitted RNA viruses with poorly understood cellular tropism and species selectivity. Mxra8 is a receptor for multiple alphaviruses including chikungunya virus (CHIKV). We discovered that while expression of mouse, rat, chimpanzee, dog, horse, goat, sheep, and human Mxra8 enables alphavirus infection in cell culture, cattle Mxra8 does not. Cattle Mxra8 encodes a 15-amino acid insertion in its ectodomain that prevents Mxra8 binding to CHIKV. Identical insertions are present in zebu, yak, and the extinct auroch. As other Bovinae lineages contain related Mxra8 sequences, this insertion likely occurred at least 5 million years ago. Removing the Mxra8 insertion in Bovinae enhances alphavirus binding and infection, while introducing the insertion into mouse Mxra8 blocks CHIKV binding, prevents infection by multiple alphaviruses in cells, and mitigates CHIKV-induced pathogenesis in mice. Our studies on how this insertion provides resistance to CHIKV infection could facilitate countermeasures that disrupt Mxra8 interactions with alphaviruses.

PubMed: 32075743
DOI: 10.1016/j.chom.2020.01.008

実験手法

X-RAY DIFFRACTION (2.3 Å)