登録情報 データベース : PDB / ID : 6w5r 構造の表示 ダウンロードとリンクタイトル NPC1 structure in Nanodisc 要素NPC intracellular cholesterol transporter 1 詳細 キーワード TRANSPORT PROTEIN / Cholesterol Lysosome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
cyclodextrin metabolic process / cholesterol storage / membrane raft organization / intracellular cholesterol transport / intracellular lipid transport / intestinal cholesterol absorption / LDL clearance / negative regulation of epithelial cell apoptotic process / lipid transporter activity / programmed cell death ... cyclodextrin metabolic process / cholesterol storage / membrane raft organization / intracellular cholesterol transport / intracellular lipid transport / intestinal cholesterol absorption / LDL clearance / negative regulation of epithelial cell apoptotic process / lipid transporter activity / programmed cell death / bile acid metabolic process / cholesterol transport / establishment of protein localization to membrane / adult walking behavior / lysosomal transport / cholesterol efflux / negative regulation of macroautophagy / cellular response to steroid hormone stimulus / cholesterol binding / protein glycosylation / cellular response to low-density lipoprotein particle stimulus / response to cadmium ion / negative regulation of TORC1 signaling / cholesterol metabolic process / neurogenesis / liver development / cholesterol homeostasis / macroautophagy / autophagy / endocytosis / transmembrane signaling receptor activity / nuclear envelope / late endosome membrane / virus receptor activity / signaling receptor activity / gene expression / lysosome / response to xenobiotic stimulus / symbiont entry into host cell / membrane raft / lysosomal membrane / perinuclear region of cytoplasm / Golgi apparatus / endoplasmic reticulum / extracellular exosome / extracellular region / membrane / plasma membrane 類似検索 - 分子機能 NPC1-like / Niemann-Pick C1, N-terminal / Niemann-Pick C1 N terminus / Sterol-sensing domain of SREBP cleavage-activation / Protein patched/dispatched / Patched family / Sterol-sensing domain (SSD) profile. / Sterol-sensing domain 類似検索 - ドメイン・相同性 CHOLESTEROL / NPC intracellular cholesterol transporter 1 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.6 Å 詳細データ登録者 Yan, N. / Qian, H.W. / Wu, X.L. 資金援助 米国, 1件 詳細 詳細を隠す組織 認可番号 国 National Science Foundation (NSF, United States) DMR-1420541 米国
引用ジャーナル : Cell / 年 : 2020タイトル : Structural Basis of Low-pH-Dependent Lysosomal Cholesterol Egress by NPC1 and NPC2.著者 : Hongwu Qian / Xuelan Wu / Ximing Du / Xia Yao / Xin Zhao / Joyce Lee / Hongyuan Yang / Nieng Yan / 要旨 : Lysosomal cholesterol egress requires two proteins, NPC1 and NPC2, whose defects are responsible for Niemann-Pick disease type C (NPC). Here, we present systematic structural characterizations that ... Lysosomal cholesterol egress requires two proteins, NPC1 and NPC2, whose defects are responsible for Niemann-Pick disease type C (NPC). Here, we present systematic structural characterizations that reveal the molecular basis for low-pH-dependent cholesterol delivery from NPC2 to the transmembrane (TM) domain of NPC1. At pH 8.0, similar structures of NPC1 were obtained in nanodiscs and in detergent at resolutions of 3.6 Å and 3.0 Å, respectively. A tunnel connecting the N-terminal domain (NTD) and the transmembrane sterol-sensing domain (SSD) was unveiled. At pH 5.5, the NTD exhibits two conformations, suggesting the motion for cholesterol delivery to the tunnel. A putative cholesterol molecule is found at the membrane boundary of the tunnel, and TM2 moves toward formation of a surface pocket on the SSD. Finally, the structure of the NPC1-NPC2 complex at 4.0 Å resolution was obtained at pH 5.5, elucidating the molecular basis for cholesterol handoff from NPC2 to NPC1(NTD). 履歴 登録 2020年3月13日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2020年6月17日 Provider : repository / タイプ : Initial release改定 1.1 2020年7月1日 Group : Database references / カテゴリ : citation / citation_authorItem : _citation.journal_abbrev / _citation.journal_id_CSD ... _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year 改定 1.2 2020年7月22日 Group : Database references / カテゴリ : citationItem : _citation.journal_volume / _citation.page_first / _citation.page_last改定 2.0 2020年7月29日 Group : Advisory / Atomic model ... Advisory / Atomic model / Data collection / Derived calculations / Structure summary カテゴリ : atom_site / chem_comp ... atom_site / chem_comp / database_PDB_caveat / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / pdbx_validate_chiral / pdbx_validate_close_contact / struct_asym / struct_conn / struct_site / struct_site_gen Item : _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ... _atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_asym_id / _atom_site.auth_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.label_entity_id / _atom_site.type_symbol / _chem_comp.name / _database_PDB_caveat.text / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_validate_chiral.auth_asym_id / _pdbx_validate_chiral.auth_seq_id / _pdbx_validate_close_contact.auth_asym_id_1 / _pdbx_validate_close_contact.auth_asym_id_2 / _pdbx_validate_close_contact.auth_seq_id_1 / _pdbx_validate_close_contact.auth_seq_id_2 / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id 解説 : Carbohydrate remediation / Provider : repository / タイプ : Remediation
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