登録情報 データベース : EMDB / ID : EMD-26701 ダウンロードとリンクタイトル Cryo-EM structure of the human Exostosin-1 and Exostosin-2 heterodimer in complex with UDP-GlcNAc マップデータsharp by deepemhancer 詳細 試料複合体 : hEXT1/2タンパク質・ペプチド : Exostosin-1タンパク質・ペプチド : Exostosin-2リガンド : URIDINE-5'-DIPHOSPHATEリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranoseリガンド : MANGANESE (II) ION 詳細機能・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
glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase / N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase / hypersensitivity / heart field specification / lymphocyte adhesion to endothelial cell of high endothelial venule / heparan sulfate N-acetylglucosaminyltransferase activity / glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity / N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity / smoothened signaling pathway involved in lung development / developmental growth involved in morphogenesis ... glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase / N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase / hypersensitivity / heart field specification / lymphocyte adhesion to endothelial cell of high endothelial venule / heparan sulfate N-acetylglucosaminyltransferase activity / glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity / N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity / smoothened signaling pathway involved in lung development / developmental growth involved in morphogenesis / sweat gland development / perichondral bone morphogenesis / mesenchymal cell differentiation involved in bone development / response to leukemia inhibitory factor / UDP-N-acetylglucosamine transferase complex / chondroitin sulfate metabolic process / response to heparin / chondrocyte hypertrophy / embryonic skeletal joint development / hematopoietic stem cell migration to bone marrow / heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process / fluid transport / glucuronosyltransferase activity / limb joint morphogenesis / tight junction organization / heparin biosynthetic process / Defective EXT2 causes exostoses 2 / Defective EXT1 causes exostoses 1, TRPS2 and CHDS / stomach development / sebaceous gland development / glomerular basement membrane development / heparan sulfate proteoglycan biosynthetic process / HS-GAG biosynthesis / glycosaminoglycan biosynthetic process / lymphocyte migration into lymphoid organs / dendrite self-avoidance / hematopoietic stem cell homeostasis / chondrocyte proliferation / glandular epithelial cell differentiation / dendritic cell migration / endochondral bone morphogenesis / sulfation / endochondral bone growth / podocyte differentiation / sodium ion homeostasis / acetylglucosaminyltransferase activity / basement membrane organization / cartilage development involved in endochondral bone morphogenesis / polysaccharide biosynthetic process / cranial skeletal system development / vocalization behavior / stem cell division / olfactory bulb development / vacuole organization / multicellular organismal-level water homeostasis / leukocyte tethering or rolling / response to light intensity / endoderm development / endochondral ossification / fear response / regulation of tumor necrosis factor-mediated signaling pathway / protein N-linked glycosylation / cellular response to fibroblast growth factor stimulus / collagen fibril organization / neural crest cell differentiation / ossification involved in bone maturation / motor behavior / cell adhesion mediated by integrin / optic nerve development / hair follicle morphogenesis / epithelial tube branching involved in lung morphogenesis / cell fate commitment / heart contraction / BMP signaling pathway / glycosyltransferase activity / protein glycosylation / mesoderm development / antigen processing and presentation / social behavior / mesoderm formation / catalytic complex / hematopoietic stem cell differentiation / canonical Wnt signaling pathway / blood vessel remodeling / fibroblast growth factor receptor signaling pathway / chondrocyte differentiation / bone resorption / ossification / gastrulation / synaptic transmission, glutamatergic / axon guidance / regulation of blood pressure / wound healing / protein catabolic process / vasodilation / multicellular organism growth / cellular response to virus / gene expression / protein-containing complex assembly / protein heterodimerization activity 類似検索 - 分子機能 Exostosin-like / Exostosin, GT47 domain / Exostosin family / Glycosyl transferase 64 domain / Glycosyl transferase family 64 domain / Nucleotide-diphospho-sugar transferases 類似検索 - ドメイン・相同性生物種 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 : 3.3 Å 詳細 データ登録者Li H 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Cancer Institute (NIH/NCI) CA231466 米国
引用ジャーナル : Nat Chem Biol / 年 : 2023タイトル : Structural basis for heparan sulfate co-polymerase action by the EXT1-2 complex.著者 : Hua Li / Digantkumar Chapla / Robert A Amos / Annapoorani Ramiah / Kelley W Moremen / Huilin Li / 要旨 : Heparan sulfate (HS) proteoglycans are extended (-GlcAβ1,4GlcNAcα1,4-) co-polymers containing decorations of sulfation and epimerization that are linked to cell surface and extracellular matrix ... Heparan sulfate (HS) proteoglycans are extended (-GlcAβ1,4GlcNAcα1,4-) co-polymers containing decorations of sulfation and epimerization that are linked to cell surface and extracellular matrix proteins. In mammals, HS repeat units are extended by an obligate heterocomplex of two exostosin family members, EXT1 and EXT2, where each protein monomer contains distinct GT47 (GT-B fold) and GT64 (GT-A fold) glycosyltransferase domains. In this study, we generated human EXT1-EXT2 (EXT1-2) as a functional heterocomplex and determined its structure in the presence of bound donor and acceptor substrates. Structural data and enzyme activity of catalytic site mutants demonstrate that only two of the four glycosyltransferase domains are major contributors to co-polymer syntheses: the EXT1 GT-B fold β1,4GlcA transferase domain and the EXT2 GT-A fold α1,4GlcNAc transferase domain. The two catalytic sites are over 90 Å apart, indicating that HS is synthesized by a dissociative process that involves a single catalytic site on each monomer. 履歴 登録 2022年4月20日 - ヘッダ(付随情報) 公開 2022年9月28日 - マップ公開 2022年9月28日 - 更新 2023年5月17日 - 現状 2023年5月17日 処理サイト : RCSB / 状態 : 公開
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