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-Structure paper
タイトル | Synergistic activation of the insulin receptor via two distinct sites. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 29, Issue 4, Page 357-368, Year 2022 |
掲載日 | 2022年3月31日 |
著者 | Jie Li / Junhee Park / John P Mayer / Kristofor J Webb / Emiko Uchikawa / Jiayi Wu / Shun Liu / Xuewu Zhang / Michael H B Stowell / Eunhee Choi / Xiao-Chen Bai / |
PubMed 要旨 | Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional ...Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional roles of each binding event during IR activation remain unresolved. Here, we showed that IR incompletely saturated with insulin predominantly forms an asymmetric conformation and exhibits partial activation. IR with one insulin bound adopts a Γ-shaped conformation. IR with two insulins bound assumes a Ƭ-shaped conformation. One insulin binds at site-1 and another simultaneously contacts both site-1 and site-2 in the Ƭ-shaped IR dimer. We further show that concurrent binding of four insulins to sites-1 and -2 prevents the formation of asymmetric IR and promotes the T-shaped symmetric, fully active state. Collectively, our results demonstrate how the synergistic binding of multiple insulins promotes optimal IR activation. |
リンク | Nat Struct Mol Biol / PubMed:35361965 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.1 - 5.0 Å |
構造データ | EMDB-25188, PDB-7sl1: EMDB-25189, PDB-7sl2: EMDB-25190, PDB-7sl3: EMDB-25191, PDB-7sl4: EMDB-25192, PDB-7sl6: EMDB-25193, PDB-7sl7: EMDB-25428, PDB-7sth: EMDB-25429, PDB-7sti: EMDB-25430, PDB-7stj: EMDB-25431, PDB-7stk: |
由来 |
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キーワード | SIGNALING PROTEIN/HORMONE / insulin receptor / site 1 binding deficient mutant insulin / SIGNALING PROTEIN / SIGNALING PROTEIN-HORMONE complex / site 2 binding deficient mutant insulin |