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データを開く
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基本情報
| 登録情報 | データベース: PDB / ID: 9p6s | ||||||||||||||||||||||||||||||
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| タイトル | Cryo-EM structure of human integrin alpha5beta1 in complex with fibronectin (FN 7-10) | ||||||||||||||||||||||||||||||
要素 |
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キーワード | CELL ADHESION / a5b1 integrin / fibronectin / extracellular matrix / focal adhesion / single-particle | ||||||||||||||||||||||||||||||
| 機能・相同性 | 機能・相同性情報integrin alpha8-beta1 complex / myoblast fate specification / integrin alpha3-beta1 complex / integrin alpha5-beta1 complex / integrin alpha6-beta1 complex / integrin alpha7-beta1 complex / integrin alpha10-beta1 complex / integrin alpha11-beta1 complex / positive regulation of glutamate uptake involved in transmission of nerve impulse / integrin alpha9-beta1 complex ...integrin alpha8-beta1 complex / myoblast fate specification / integrin alpha3-beta1 complex / integrin alpha5-beta1 complex / integrin alpha6-beta1 complex / integrin alpha7-beta1 complex / integrin alpha10-beta1 complex / integrin alpha11-beta1 complex / positive regulation of glutamate uptake involved in transmission of nerve impulse / integrin alpha9-beta1 complex / cardiac cell fate specification / regulation of collagen catabolic process / cell adhesion receptor activity / integrin alpha1-beta1 complex / integrin binding involved in cell-matrix adhesion / integrin alpha4-beta1 complex / collagen binding involved in cell-matrix adhesion / integrin alpha2-beta1 complex / Localization of the PINCH-ILK-PARVIN complex to focal adhesions / cell-cell adhesion mediated by integrin / formation of radial glial scaffolds / negative regulation of monocyte activation / Other semaphorin interactions / Formation of the ureteric bud / negative regulation of transforming growth factor beta production / cerebellar climbing fiber to Purkinje cell synapse / positive regulation of substrate-dependent cell migration, cell attachment to substrate / CD40 signaling pathway / calcium-independent cell-matrix adhesion / positive regulation of fibroblast growth factor receptor signaling pathway / neural crest cell migration involved in autonomic nervous system development / reactive gliosis / myelin sheath abaxonal region / integrin alphav-beta1 complex / CHL1 interactions / fibrinogen complex / regulation of synapse pruning / basement membrane organization / cardiac muscle cell myoblast differentiation / RUNX2 regulates genes involved in cell migration / Fibronectin matrix formation / alphav-beta3 integrin-vitronectin complex / Attachment of bacteria to epithelial cells / MET interacts with TNS proteins / Laminin interactions / enteric nervous system development / Platelet Adhesion to exposed collagen / Developmental Lineage of Mammary Stem Cells / integrin activation / germ cell migration / leukocyte tethering or rolling / vascular endothelial growth factor receptor 2 binding / ALK mutants bind TKIs / positive regulation of vascular endothelial growth factor signaling pathway / cell migration involved in sprouting angiogenesis / myoblast fusion / positive regulation of cell-substrate adhesion / axon extension / Elastic fibre formation / cell-substrate junction assembly / cardiac muscle cell differentiation / platelet-derived growth factor receptor binding / myoblast differentiation / mesodermal cell differentiation / Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin / central nervous system neuron differentiation / proteoglycan binding / positive regulation of vascular endothelial growth factor receptor signaling pathway / cell projection organization / wound healing, spreading of epidermal cells / heterophilic cell-cell adhesion / positive regulation of fibroblast migration / integrin complex / regulation of spontaneous synaptic transmission / negative regulation of Rho protein signal transduction / cell adhesion mediated by integrin / MET activates PTK2 signaling / heterotypic cell-cell adhesion / Molecules associated with elastic fibres / Basigin interactions / epidermal growth factor receptor binding / lamellipodium assembly / peptidase activator activity / negative regulation of vasoconstriction / neural crest cell migration / muscle organ development / Mechanical load activates signaling by PIEZO1 and integrins in osteocytes / leukocyte cell-cell adhesion / Syndecan interactions / extracellular matrix structural constituent / sarcomere organization / p130Cas linkage to MAPK signaling for integrins / dendrite morphogenesis / biological process involved in interaction with symbiont / positive regulation of neuroblast proliferation / positive regulation of wound healing / negative regulation of neuron differentiation / response to muscle activity / positive regulation of sprouting angiogenesis / regulation of protein phosphorylation 類似検索 - 分子機能 | ||||||||||||||||||||||||||||||
| 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: 2.61 Å | ||||||||||||||||||||||||||||||
データ登録者 | Ding, J. / Fantini, D. / Dedden, D. / Schumacher, S. / Biertumpfel, C. / Mizuno, N. | ||||||||||||||||||||||||||||||
| 資金援助 | 米国, 1件
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引用 | ジャーナル: PNAS Nexus / 年: 2026タイトル: Allosteric regulation of fibronectin binding by the anti-β1 integrin antibody TS2/16. 著者: Jienyu Ding / Dalia A Fantini / Dirk Dedden / Stephanie Schumacher / Christian Biertümpfel / Naoko Mizuno / ![]() 要旨: The monoclonal antibody (mAb) TS2/16 stabilizes the active conformation of β1 integrin, enhancing its adhesive capacity on the cell surface. However, the molecular mechanism by which TS2/16 ...The monoclonal antibody (mAb) TS2/16 stabilizes the active conformation of β1 integrin, enhancing its adhesive capacity on the cell surface. However, the molecular mechanism by which TS2/16 modulates integrin affinity for extracellular ligands remains unclear. Using endogenous full-length α5β1 integrin purified from human placenta, we determined the structure of integrin α5β1 with fibronectin up to 2.61-Å resolution in the absence of TS2/16, capturing the active form without its aid, and performed comparative B-factor-based analysis and CABS-Flex simulation with and without TS2/16. Despite no global conformational differences, we found that TS2/16 interacts with α2 helix of the integrin β1 subunit and contacts the C-terminus of α3 helix, leading to a localized decrease in B factor. This interaction allosterically alters the dynamics of α2-α3 loop despite not being in direct contact with TS2/16. Notably, this loop directly engages fibronectin, and its dynamic change underlies the enhanced ligand-binding affinity and explains increased cell adhesion observed with TS2/16. These findings reveal an allosteric mechanism of integrin regulation by TS2/16 and offer insights for the rational design of therapeutic antibodies targeting integrin-mediated adhesion in pathological contexts such as inflammation and cancer. | ||||||||||||||||||||||||||||||
| 履歴 |
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構造の表示
| 構造ビューア | 分子: Molmil Jmol/JSmol |
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ダウンロードとリンク
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ダウンロード
| PDBx/mmCIF形式 | 9p6s.cif.gz | 262.5 KB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb9p6s.ent.gz | 204 KB | 表示 | PDB形式 |
| PDBx/mmJSON形式 | 9p6s.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/p6/9p6s ftp://data.pdbj.org/pub/pdb/validation_reports/p6/9p6s | HTTPS FTP |
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-関連構造データ
| 関連構造データ | ![]() 71324MC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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| 類似構造データ | 類似検索 - 機能・相同性 F&H 検索 |
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リンク
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集合体
| 登録構造単位 | ![]()
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要素
-タンパク質 , 3種, 3分子 ABC
| #1: タンパク質 | 分子量: 64733.770 Da / 分子数: 1 / 由来タイプ: 天然 / 詳細: processed (signal peptide is cleaved) / 由来: (天然) Homo sapiens (ヒト) / 器官: placenta / 参照: UniProt: P08648 |
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| #2: タンパク質 | 分子量: 48952.363 Da / 分子数: 1 / 由来タイプ: 天然 / 詳細: processed (signal peptide is cleaved) / 由来: (天然) Homo sapiens (ヒト) / 器官: placenta / 参照: UniProt: P05556 |
| #3: タンパク質 | 分子量: 19849.061 Da / 分子数: 1 / 由来タイプ: 組換発現 / 詳細: truncated to domains FN7-10 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: FN1, FN / 発現宿主: ![]() |
-糖 , 5種, 11分子 
| #4: 多糖 | | #5: 多糖 | alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #6: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #7: 多糖 | #9: 糖 | ChemComp-NAG / |
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-非ポリマー , 2種, 34分子 


| #8: 化合物 | ChemComp-MN / #10: 水 | ChemComp-HOH / | |
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-詳細
| 研究の焦点であるリガンドがあるか | N |
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| Has protein modification | Y |
-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 |
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試料調製
| 構成要素 | 名称: integrin a5b1-fibronectin complex / タイプ: COMPLEX / Entity ID: #1-#3 / 由来: NATURAL |
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| 分子量 | 実験値: NO |
| 由来(天然) | 生物種: Homo sapiens (ヒト) / 器官: placenta |
| 緩衝液 | pH: 7.5 |
| 試料 | 濃度: 1.9 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: integrin a5b1 in nanodiscs (MSPE3D1) was incubated with 10 mM MnCl2 for 30 min at 4C, then mixed with purified FN7-10 at a molar ratio of 1:3, at a final a5b1-ND concentration of 0.15 mg/ml ...詳細: integrin a5b1 in nanodiscs (MSPE3D1) was incubated with 10 mM MnCl2 for 30 min at 4C, then mixed with purified FN7-10 at a molar ratio of 1:3, at a final a5b1-ND concentration of 0.15 mg/ml in TBS pH 7.5 and 1 mM MnCl2. |
| 試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 200 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
| 急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE-PROPANE / 湿度: 100 % / 凍結前の試料温度: 277 K |
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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: TFS 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 FIELD / 倍率(公称値): 105000 X / 最大 デフォーカス(公称値): 3200 nm / 最小 デフォーカス(公称値): 500 nm / Cs: 2.62 mm / C2レンズ絞り径: 70 µm / アライメント法: COMA FREE |
| 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: 69 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 10341 |
| 電子光学装置 | エネルギーフィルター名称: GIF Bioquantum / エネルギーフィルタースリット幅: 20 eV |
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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: 2640989 | ||||||||||||||||||||||||||||||||||||||||||||||||
| 対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||||||||||||||
| 3次元再構成 | 解像度: 2.61 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 130907 / アルゴリズム: FOURIER SPACE / クラス平均像の数: 1 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||
| 原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: REAL 詳細: initial rigid body fitting in chimera, then cycles of manual adjustment/modeling in coot and real-space refinement in phenix | ||||||||||||||||||||||||||||||||||||||||||||||||
| 原子モデル構築 | 3D fitting-ID: 1 / Source name: PDB / タイプ: experimental model
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| 精密化 | 最高解像度: 2.61 Å / 交差検証法: NONE 立体化学のターゲット値: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) | ||||||||||||||||||||||||||||||||||||||||||||||||
| 拘束条件 |
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万見について




Homo sapiens (ヒト)
米国, 1件
引用


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light scattering



