- EMDB-26181: Cryo-EM Structure of insulin receptor-related receptor (IRR) in a... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-26181
タイトル
Cryo-EM Structure of insulin receptor-related receptor (IRR) in apo-state captured at pH 7. The 3D refinement was focused on one of two halves with C1 symmetry applied
マップデータ
Cryo-EM Structure of insulin receptor-related receptor (IRR) in apo-state captured at pH 7. The 3D refinement was focused on one of two halves with C1 symmetry applied.
試料
複合体: Insulin receptor-related receptor (IRR) in apo-state captured at pH 7
タンパク質・ペプチド: Insulin receptor-related protein
キーワード
Receptor tyrosine kinase / insulin receptor family / SIGNALING PROTEIN
機能・相同性
機能・相同性情報
cellular response to alkaline pH / male sex determination / insulin receptor complex / insulin receptor activity / insulin receptor substrate binding / phosphatidylinositol 3-kinase binding / cell surface receptor protein tyrosine kinase signaling pathway / transmembrane receptor protein tyrosine kinase activity / receptor protein-tyrosine kinase / actin cytoskeleton organization ...cellular response to alkaline pH / male sex determination / insulin receptor complex / insulin receptor activity / insulin receptor substrate binding / phosphatidylinositol 3-kinase binding / cell surface receptor protein tyrosine kinase signaling pathway / transmembrane receptor protein tyrosine kinase activity / receptor protein-tyrosine kinase / actin cytoskeleton organization / protein autophosphorylation / receptor complex / axon / ATP binding / plasma membrane 類似検索 - 分子機能
Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats ...Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats / Growth factor receptor cysteine-rich domain superfamily / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM136976
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35GM142937
米国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2023 タイトル: Structural basis of the alkaline pH-dependent activation of insulin receptor-related receptor. 著者: Liwei Wang / Catherine Hall / Jie Li / Eunhee Choi / Xiao-Chen Bai / 要旨: The insulin receptor (IR) family is a subfamily of receptor tyrosine kinases that controls metabolic homeostasis and cell growth. Distinct from IR and insulin-like growth factor 1 receptor, whose ...The insulin receptor (IR) family is a subfamily of receptor tyrosine kinases that controls metabolic homeostasis and cell growth. Distinct from IR and insulin-like growth factor 1 receptor, whose activation requires ligand binding, insulin receptor-related receptor (IRR)-the third member of the IR family-is activated by alkaline pH. However, the molecular mechanism underlying alkaline pH-induced IRR activation remains unclear. Here, we present cryo-EM structures of human IRR in both neutral pH inactive and alkaline pH active states. Combined with mutagenesis and cellular assays, we show that, upon pH increase, electrostatic repulsion of the pH-sensitive motifs of IRR disrupts its autoinhibited state and promotes a scissor-like rotation between two protomers, leading to a T-shaped active conformation. Together, our study reveals an unprecedented alkaline pH-dependent activation mechanism of IRR, opening up opportunities to understand the structure-function relationship of this important receptor.
ダウンロード / ファイル: emd_26181.map.gz / 形式: CCP4 / 大きさ: 52.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Cryo-EM Structure of insulin receptor-related receptor (IRR) in apo-state captured at pH 7. The 3D refinement was focused on one of two halves with C1 symmetry applied.
ボクセルのサイズ
X=Y=Z: 1.08 Å
密度
表面レベル
登録者による: 0.03
最小 - 最大
-0.11890141 - 0.19619457
平均 (標準偏差)
-0.000046182773 (±0.0046595773)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
0
0
0
サイズ
240
240
240
Spacing
240
240
240
セル
A=B=C: 259.2 Å α=β=γ: 90.0 °
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添付データ
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ハーフマップ: Cryo-EM Structure of insulin receptor-related receptor (IRR) in...
Cryo-EM Structure of insulin receptor-related receptor (IRR) in apo-state captured at pH 7. The 3D refinement was focused on one of two halves with C1 symmetry applied. Unfiltered half2 map
Cryo-EM Structure of insulin receptor-related receptor (IRR) in apo-state captured at pH 7. The 3D refinement was focused on one of two halves with C1 symmetry applied. Unfiltered half1 map
PDB-7tyj: Cryo-EM Structure of insulin receptor-related receptor (IRR) in apo-state captured at pH 7. The 3D refinement was focused on one of two halves with C1 symmetry applied