+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7m0r | ||||||||||||||||||
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タイトル | Cryo-EM structure of the Sema3A/PlexinA4/Neuropilin 1 complex | ||||||||||||||||||
要素 |
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キーワード | SIGNALING PROTEIN / plexin / semaphorin (セマフォリン) / neuropilin / signaling | ||||||||||||||||||
機能・相同性 | 機能・相同性情報 Neurophilin interactions with VEGF and VEGFR / neural crest cell migration involved in sympathetic nervous system development / glossopharyngeal nerve morphogenesis / chemorepulsion of branchiomotor axon / regulation of negative chemotaxis / vagus nerve morphogenesis / cell migration involved in coronary vasculogenesis / anterior commissure morphogenesis / cranial nerve morphogenesis / trigeminal nerve morphogenesis ...Neurophilin interactions with VEGF and VEGFR / neural crest cell migration involved in sympathetic nervous system development / glossopharyngeal nerve morphogenesis / chemorepulsion of branchiomotor axon / regulation of negative chemotaxis / vagus nerve morphogenesis / cell migration involved in coronary vasculogenesis / anterior commissure morphogenesis / cranial nerve morphogenesis / trigeminal nerve morphogenesis / Signal transduction by L1 / regulation of axon extension involved in axon guidance / postganglionic parasympathetic fiber development / synaptic target recognition / facial nerve morphogenesis / sympathetic neuron axon guidance / CRMPs in Sema3A signaling / basal dendrite development / protein localization to early endosome / otic placode development / ニューロフィラメント / basal dendrite arborization / Sema3A PAK dependent Axon repulsion / dichotomous subdivision of terminal units involved in salivary gland branching / retina vasculature morphogenesis in camera-type eye / regulation of vascular endothelial growth factor receptor signaling pathway / vestibulocochlear nerve structural organization / semaphorin receptor binding / dorsal root ganglion morphogenesis / epithelial cell migration / ventral trunk neural crest cell migration / sympathetic neuron projection guidance / facioacoustic ganglion development / trigeminal ganglion development / cerebellar climbing fiber to Purkinje cell synapse / trigeminal nerve structural organization / sensory neuron axon guidance / facial nerve structural organization / gonadotrophin-releasing hormone neuronal migration to the hypothalamus / postsynapse organization / branchiomotor neuron axon guidance / renal artery morphogenesis / positive regulation of male gonad development / SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion / semaphorin-plexin signaling pathway involved in axon guidance / maintenance of synapse structure / axon extension involved in axon guidance / VEGF-activated neuropilin signaling pathway / negative regulation of axon extension involved in axon guidance / retina vasculature development in camera-type eye / blood vessel endothelial cell migration / sympathetic neuron projection extension / negative regulation of epithelial cell migration / motor neuron migration / endothelial cell chemotaxis / vascular endothelial growth factor binding / sympathetic ganglion development / axonogenesis involved in innervation / neural crest cell migration involved in autonomic nervous system development / positive regulation of axon extension involved in axon guidance / negative regulation of axon extension / vascular endothelial growth factor receptor activity / substrate-dependent cell migration, cell extension / nerve development / semaphorin receptor complex / positive regulation of neuron migration / angiogenesis involved in coronary vascular morphogenesis / olfactory bulb development / sympathetic nervous system development / hepatocyte growth factor receptor signaling pathway / neuropilin signaling pathway / neuropilin binding / coronary artery morphogenesis / outflow tract septum morphogenesis / regulation of Cdc42 protein signal transduction / chemorepellent activity / semaphorin receptor activity / commissural neuron axon guidance / embryonic heart tube development / negative regulation of cell adhesion / axon extension / motor neuron axon guidance / retinal ganglion cell axon guidance / cell migration involved in sprouting angiogenesis / artery morphogenesis / axonal fasciculation / dendrite morphogenesis / 血管新生 / 神経堤 / positive regulation of filopodium assembly / negative chemotaxis / branching involved in blood vessel morphogenesis / cellular response to hepatocyte growth factor stimulus / positive regulation of axonogenesis / positive regulation of cell migration involved in sprouting angiogenesis / positive chemotaxis / dendrite development / growth factor binding / sorting endosome / positive regulation of focal adhesion assembly 類似検索 - 分子機能 | ||||||||||||||||||
生物種 | Mus musculus (ハツカネズミ) | ||||||||||||||||||
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: 3.7 Å | ||||||||||||||||||
データ登録者 | Lu, D. / Shang, G. / He, X. / Bai, X. / Zhang, X. | ||||||||||||||||||
資金援助 | 米国, 5件
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引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex. 著者: Defen Lu / Guijun Shang / Xiaojing He / Xiao-Chen Bai / Xuewu Zhang / 要旨: Secreted class 3 semaphorins (Sema3s) form tripartite complexes with the plexin receptor and neuropilin coreceptor, which are both transmembrane proteins that together mediate semaphorin signal for ...Secreted class 3 semaphorins (Sema3s) form tripartite complexes with the plexin receptor and neuropilin coreceptor, which are both transmembrane proteins that together mediate semaphorin signal for neuronal axon guidance and other processes. Despite extensive investigations, the overall architecture of and the molecular interactions in the Sema3/plexin/neuropilin complex are incompletely understood. Here we present the cryo-EM structure of a near intact extracellular region complex of Sema3A, PlexinA4 and Neuropilin 1 (Nrp1) at 3.7 Å resolution. The structure shows a large symmetric 2:2:2 assembly in which each subunit makes multiple interactions with others. The two PlexinA4 molecules in the complex do not interact directly, but their membrane proximal regions are close to each other and poised to promote the formation of the intracellular active dimer for signaling. The structure reveals a previously unknown interface between the a2b1b2 module in Nrp1 and the Sema domain of Sema3A. This interaction places the a2b1b2 module at the top of the complex, far away from the plasma membrane where the transmembrane regions of Nrp1 and PlexinA4 embed. As a result, the region following the a2b1b2 module in Nrp1 must span a large distance to allow the connection to the transmembrane region, suggesting an essential role for the long non-conserved linkers and the MAM domain in neuropilin in the semaphorin/plexin/neuropilin complex. | ||||||||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7m0r.cif.gz | 725.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7m0r.ent.gz | 575.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7m0r.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/m0/7m0r ftp://data.pdbj.org/pub/pdb/validation_reports/m0/7m0r | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 64132.211 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Nrp1, Nrp / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P97333 #2: タンパク質 | 分子量: 67931.812 Da / 分子数: 2 / Mutation: A106K,551ARTRA555,731AAQAA735,758ANRA761 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Sema3a, Semad, SemD / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: O08665 #3: タンパク質 | 分子量: 133253.203 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Plxna4, Kiaa1550 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q80UG2 #4: 化合物 | ChemComp-CA / 研究の焦点であるリガンドがあるか | N | 配列の詳細 | The full sequence of Semaphorin-3A is NYANGKNNVPRLKLSYKEMLESNNVITFNGLANSSSYHTFLLDEERSRLYVGAKDHIFSF ...The full sequence of Semaphorin-3A is NYANGKNNVP | |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Ternary complex of Sema3A, PlexinA4 and neuropilin 1 タイプ: COMPLEX / Entity ID: #1-#3 / 由来: RECOMBINANT |
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分子量 | 値: 600 kDa/nm / 実験値: YES |
由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / C2レンズ絞り径: 100 µm |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 1453090 | ||||||||||||||||||||||||
対称性 | 点対称性: C2 (2回回転対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 26741 / 対称性のタイプ: POINT |