EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Activation of the insulin receptor by insulin-like growth factor 2.
ジャーナル・号・ページ	Nat Commun, Vol. 15, Issue 1, Page 2609, Year 2024
掲載日	2024年3月23日
著者	Weidong An / Catherine Hall / Jie Li / Albert Hung / Jiayi Wu / Junhee Park / Liwei Wang / Xiao-Chen Bai / Eunhee Choi /
PubMed 要旨	Insulin receptor (IR) controls growth and metabolism. Insulin-like growth factor 2 (IGF2) has different binding properties on two IR isoforms, mimicking insulin's function. However, the molecular ...Insulin receptor (IR) controls growth and metabolism. Insulin-like growth factor 2 (IGF2) has different binding properties on two IR isoforms, mimicking insulin's function. However, the molecular mechanism underlying IGF2-induced IR activation remains unclear. Here, we present cryo-EM structures of full-length human long isoform IR (IR-B) in both the inactive and IGF2-bound active states, and short isoform IR (IR-A) in the IGF2-bound active state. Under saturated IGF2 concentrations, both the IR-A and IR-B adopt predominantly asymmetric conformations with two or three IGF2s bound at site-1 and site-2, which differs from that insulin saturated IR forms an exclusively T-shaped symmetric conformation. IGF2 exhibits a relatively weak binding to IR site-2 compared to insulin, making it less potent in promoting full IR activation. Cell-based experiments validated the functional importance of IGF2 binding to two distinct binding sites in optimal IR signaling and trafficking. In the inactive state, the C-terminus of α-CT of IR-B contacts FnIII-2 domain of the same protomer, hindering its threading into the C-loop of IGF2, thus reducing the association rate of IGF2 with IR-B. Collectively, our studies demonstrate the activation mechanism of IR by IGF2 and reveal the molecular basis underlying the different affinity of IGF2 to IR-A and IR-B.
リンク	Nat Commun / PubMed:38521788 / PubMed Central
手法	EM (単粒子)
解像度	3.6 - 4.2 Å
構造データ	41877 8u4b EMDB-41877, PDB-8u4b: Cryo-EM structure of long form insulin receptor (IR-B) in the apo state 手法: EM (単粒子) / 解像度: 3.9 Å 41878 8u4c EMDB-41878, PDB-8u4c: Cryo-EM structure of long form insulin receptor (IR-B) with four IGF2 bound, symmetric conformation. 手法: EM (単粒子) / 解像度: 3.6 Å 41880 8u4e EMDB-41880, PDB-8u4e: Cryo-EM structure of long form insulin receptor (IR-B) with three IGF2 bound, asymmetric conformation. 手法: EM (単粒子) / 解像度: 4.2 Å 43279 8vjb EMDB-43279, PDB-8vjb: Cryo-EM structure of short form insulin receptor (IR-A) with four IGF2 bound, symmetric conformation. 手法: EM (単粒子) / 解像度: 3.6 Å 43280 8vjc EMDB-43280, PDB-8vjc: Cryo-EM structure of short form insulin receptor (IR-A) with three IGF2 bound, asymmetric conformation. 手法: EM (単粒子) / 解像度: 3.8 Å
由来	homo sapiens (ヒト)
キーワード	SIGNALING PROTEIN / Insulin receptor / IGF2 / RTK