登録情報 データベース : EMDB / ID : EMD-26702 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-GlcA 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リガンド : URIDINE-5'-DIPHOSPHATE 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 / 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 / chondrocyte hypertrophy / embryonic skeletal joint development / hematopoietic stem cell migration to bone marrow / fluid transport / : / limb joint morphogenesis / tight junction organization / glucuronosyltransferase activity / Defective EXT2 causes exostoses 2 / Defective EXT1 causes exostoses 1, TRPS2 and CHDS / heparin proteoglycan biosynthetic process / stomach development / sebaceous gland development / response to heparin / glomerular basement membrane development / glycosaminoglycan biosynthetic process / HS-GAG biosynthesis / lymphocyte migration into lymphoid organs / sulfation / heparan sulfate proteoglycan biosynthetic process / chondrocyte proliferation / dendritic cell migration / endochondral bone morphogenesis / dendrite self-avoidance / glandular epithelial cell differentiation / hematopoietic stem cell homeostasis / endochondral bone growth / acetylglucosaminyltransferase activity / podocyte differentiation / sodium ion homeostasis / cartilage development involved in endochondral bone morphogenesis / basement membrane organization / vocalization behavior / cranial skeletal system development / vacuole organization / olfactory bulb development / leukocyte tethering or rolling / endochondral ossification / multicellular organismal-level water homeostasis / endoderm development / polysaccharide biosynthetic process / fear response / stem cell division / response to light intensity / protein N-linked glycosylation / regulation of tumor necrosis factor-mediated signaling pathway / collagen fibril organization / neural crest cell differentiation / ossification involved in bone maturation / motor behavior / optic nerve development / hair follicle morphogenesis / cell adhesion mediated by integrin / epithelial tube branching involved in lung morphogenesis / heart contraction / protein glycosylation / antigen processing and presentation / glycosyltransferase activity / mesoderm development / social behavior / mesoderm formation / cellular response to fibroblast growth factor stimulus / blood vessel remodeling / catalytic complex / cell fate commitment / fibroblast growth factor receptor signaling pathway / hematopoietic stem cell differentiation / canonical Wnt signaling pathway / chondrocyte differentiation / BMP signaling pathway / bone resorption / gastrulation / ossification / axon guidance / synaptic transmission, glutamatergic / wound healing / protein catabolic process / multicellular organism growth / cellular response to virus / regulation of blood pressure / 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 : 3.0 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 2024年11月6日 - 現状 2024年11月6日 処理サイト : RCSB / 状態 : 公開
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