登録情報 データベース : EMDB / ID : EMD-9108 構造の表示 ダウンロードとリンクタイトル Structural basis of coreceptor recognition by HIV-1 envelope spike マップデータHIV-1 envelope spike 詳細 試料複合体 : C-C chemokine receptor type 5 (CCR5) in complex with T-cell surface glycoprotein CD4 and HIV1 envelope glycoprotein gp120複合体 : Envelope glycoprotein gp160タンパク質・ペプチド : Envelope glycoprotein gp160複合体 : T-cell surface glycoprotein CD4タンパク質・ペプチド : T-cell surface glycoprotein CD4複合体 : C-C chemokine receptor type 5タンパク質・ペプチド : C-C chemokine receptor type 5リガンド : 2-acetamido-2-deoxy-beta-D-glucopyranoseリガンド : beta-D-mannopyranoseリガンド : 2-acetamido-2-deoxy-alpha-D-galactopyranose 詳細 キーワード HIV coreceptor / MEMBRANE PROTEIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
chemokine (C-C motif) ligand 5 binding / negative regulation of macrophage apoptotic process / chemokine receptor activity / helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / signaling / T cell selection / MHC class II protein binding ... chemokine (C-C motif) ligand 5 binding / negative regulation of macrophage apoptotic process / chemokine receptor activity / helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / signaling / T cell selection / MHC class II protein binding / C-C chemokine receptor activity / phosphatidylinositol-4,5-bisphosphate phospholipase C activity / positive regulation of kinase activity / cellular response to granulocyte macrophage colony-stimulating factor stimulus / C-C chemokine binding / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / response to cholesterol / Nef Mediated CD4 Down-regulation / Alpha-defensins / regulation of T cell activation / Chemokine receptors bind chemokines / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / Other interleukin signaling / dendritic cell chemotaxis / extracellular matrix structural constituent / T cell receptor complex / enzyme-linked receptor protein signaling pathway / Interleukin-10 signaling / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / macrophage differentiation / regulation of calcium ion transport / Generation of second messenger molecules / T cell differentiation / Co-inhibition by PD-1 / positive regulation of protein kinase activity / Binding and entry of HIV virion / cellular defense response / coreceptor activity / positive regulation of interleukin-2 production / positive regulation of calcium-mediated signaling / cell surface receptor protein tyrosine kinase signaling pathway / host cell endosome membrane / protein tyrosine kinase binding / cell chemotaxis / Vpu mediated degradation of CD4 / clathrin-coated endocytic vesicle membrane / calcium-mediated signaling / positive regulation of T cell activation / chemotaxis / calcium ion transport / MHC class II protein complex binding / transmembrane signaling receptor activity / MAPK cascade / Downstream TCR signaling / Cargo recognition for clathrin-mediated endocytosis / cell-cell signaling / signaling receptor activity / Clathrin-mediated endocytosis / positive regulation of protein phosphorylation / actin binding / virus receptor activity / cellular response to lipopolysaccharide / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / defense response to Gram-negative bacterium / clathrin-dependent endocytosis of virus by host cell / adaptive immune response / positive regulation of canonical NF-kappaB signal transduction / positive regulation of viral entry into host cell / early endosome / cell surface receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / positive regulation of MAPK cascade / endosome / cell adhesion / immune response / G protein-coupled receptor signaling pathway / inflammatory response / membrane raft / endoplasmic reticulum lumen / external side of plasma membrane / fusion of virus membrane with host endosome membrane / apoptotic process / lipid binding / viral envelope / endoplasmic reticulum membrane / protein kinase binding / positive regulation of DNA-templated transcription / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / enzyme binding / cell surface / signal transduction / protein homodimerization activity / zinc ion binding / identical protein binding 類似検索 - 分子機能 CC chemokine receptor 5 / CD4, extracellular / T cell CD4 receptor C-terminal region / CD4, extracellular / T cell CD4 receptor C terminal region / T-cell surface antigen CD4 / Immunoglobulin C2-set / Immunoglobulin C2-set domain / Chemokine receptor family / : ... CC chemokine receptor 5 / CD4, extracellular / T cell CD4 receptor C-terminal region / CD4, extracellular / T cell CD4 receptor C terminal region / T-cell surface antigen CD4 / Immunoglobulin C2-set / Immunoglobulin C2-set domain / Chemokine receptor family / : / Immunoglobulin / Immunoglobulin domain / Envelope glycoprotein Gp160 / Retroviral envelope protein / Retroviral envelope protein GP41-like / Gp120 core superfamily / Envelope glycoprotein GP120 / Human immunodeficiency virus 1, envelope glycoprotein Gp120 / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Immunoglobulin V-Type / Immunoglobulin V-set domain / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold 類似検索 - ドメイン・相同性 T-cell surface glycoprotein CD4 / C-C chemokine receptor type 5 / Envelope glycoprotein gp160 類似検索 - 構成要素生物種 Human immunodeficiency virus 1 (ヒト免疫不全ウイルス) / Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.9 Å 詳細 データ登録者Shaik MM / Chen B 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI) AI141002 米国
引用ジャーナル : Nature / 年 : 2019タイトル : Structural basis of coreceptor recognition by HIV-1 envelope spike.著者 : Md Munan Shaik / Hanqin Peng / Jianming Lu / Sophia Rits-Volloch / Chen Xu / Maofu Liao / Bing Chen / 要旨 : HIV-1 envelope glycoprotein (Env), which consists of trimeric (gp160) cleaved to (gp120 and gp41), interacts with the primary receptor CD4 and a coreceptor (such as chemokine receptor CCR5) to fuse ... HIV-1 envelope glycoprotein (Env), which consists of trimeric (gp160) cleaved to (gp120 and gp41), interacts with the primary receptor CD4 and a coreceptor (such as chemokine receptor CCR5) to fuse viral and target-cell membranes. The gp120-coreceptor interaction has previously been proposed as the most crucial trigger for unleashing the fusogenic potential of gp41. Here we report a cryo-electron microscopy structure of a full-length gp120 in complex with soluble CD4 and unmodified human CCR5, at 3.9 Å resolution. The V3 loop of gp120 inserts into the chemokine-binding pocket formed by seven transmembrane helices of CCR5, and the N terminus of CCR5 contacts the CD4-induced bridging sheet of gp120. CCR5 induces no obvious allosteric changes in gp120 that can propagate to gp41; it does bring the Env trimer close to the target membrane. The N terminus of gp120, which is gripped by gp41 in the pre-fusion or CD4-bound Env, flips back in the CCR5-bound conformation and may irreversibly destabilize gp41 to initiate fusion. The coreceptor probably functions by stabilizing and anchoring the CD4-induced conformation of Env near the cell membrane. These results advance our understanding of HIV-1 entry into host cells and may guide the development of vaccines and therapeutic agents. 履歴 登録 2018年9月6日 - ヘッダ(付随情報) 公開 2018年10月10日 - マップ公開 2018年12月12日 - 更新 2024年10月23日 - 現状 2024年10月23日 処理サイト : RCSB / 状態 : 公開
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