登録情報 データベース : EMDB / ID : EMD-25035 ダウンロードとリンクタイトル Cryo-EM 3D map of the human Exostosin-1 and Exostosin-2 heterodimer マップデータ 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 詳細 キーワード exostosin1 / exostosin2 / glycosyltransferase / heparan sulfate / TRANSFERASE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 / chondroitin sulfate proteoglycan metabolic process / smoothened signaling pathway involved in lung development ... 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 / chondroitin sulfate proteoglycan metabolic process / 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 / chondrocyte hypertrophy / fluid transport / hematopoietic stem cell migration to bone marrow / chondrocyte differentiation involved in endochondral bone morphogenesis / glucuronosyltransferase activity / heparin proteoglycan biosynthetic process / tight junction organization / Defective EXT2 causes exostoses 2 / Defective EXT1 causes exostoses 1, TRPS2 and CHDS / sebaceous gland development / glomerular basement membrane development / response to heparin / stomach development / glandular epithelial cell differentiation / lymphocyte migration into lymphoid organs / glycosaminoglycan biosynthetic process / HS-GAG biosynthesis / sulfation / embryonic skeletal limb joint morphogenesis / chondrocyte proliferation / endochondral bone morphogenesis / acetylglucosaminyltransferase activity / dendritic cell migration / heparan sulfate proteoglycan biosynthetic process / dendrite self-avoidance / podocyte differentiation / endochondral bone growth / hematopoietic stem cell homeostasis / sodium ion homeostasis / limb bud formation / basement membrane organization / bone trabecula morphogenesis / olfactory bulb development / endochondral ossification / vacuole organization / multicellular organismal-level water homeostasis / cranial skeletal system development / endoderm development / leukocyte tethering or rolling / response to light intensity / vocalization behavior / fear response / protein N-linked glycosylation / polysaccharide biosynthetic process / regulation of tumor necrosis factor-mediated signaling pathway / mesodermal cell differentiation / optic nerve development / collagen fibril organization / cell adhesion mediated by integrin / ossification involved in bone maturation / hair follicle morphogenesis / stem cell division / neural crest cell differentiation / antigen processing and presentation / heart contraction / glycosyltransferase activity / epithelial tube branching involved in lung morphogenesis / motor behavior / outflow tract morphogenesis / mesoderm formation / fibroblast growth factor receptor signaling pathway / chondrocyte differentiation / cell fate commitment / blood vessel remodeling / bone resorption / hematopoietic stem cell differentiation / canonical Wnt signaling pathway / BMP signaling pathway / social behavior / catalytic complex / ERK1 and ERK2 cascade / cellular response to fibroblast growth factor stimulus / ossification / axon guidance / protein catabolic process / wound healing / synaptic transmission, glutamatergic / cellular response to virus / regulation of blood pressure / multicellular organism growth / vasodilation / protein-containing complex assembly / gene expression / protein heterodimerization activity 類似検索 - 分子機能 Exostosin-like / Exostosin, GT47 domain / Exostosin GT47 domain / 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 : 3.1 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 2021年9月28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 2024年11月20日 - 現状 2024年11月20日 処理サイト : RCSB / 状態 : 公開
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