A third fibronectin type III domain in the extracellular region of the insulin receptor family

FEBS Letters

Siddle, Kenneth²  Blundell, Tom L.¹  Marino-Buslje, Cristina¹  Mizuguchi, Kenji¹ 

[1]Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK

[2]Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Cambridge CB2 2QR, UK

关键词: Insulin receptor;    Fibronectin type III;    Signal transduction;    Comparative modeling;   

DOI  :  10.1016/S0014-5793(98)01509-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The insulin receptor family consists of the homologous tyrosine kinase receptors, insulin receptor (IR), insulin-like growth factor 1 receptor (IGF1R) and insulin receptor-related receptor. The three-dimensional structures of the tyrosine kinase domain of the IR and the first three extracellular domains (L1, Cys-rich and L2) of the IGF1R are known. Here we present evidence that the connecting domain of the IR family is a member of the fibronectin type III (FnIII) superfamily. Structure-based alignment of FnIII domains reveals several key residues that are also conserved in the sequence of the connecting domain. The alignment of the connecting domain with FnIII domains is in good agreement with secondary structure prediction. A model of the connecting domain shows a hydrophobic core formed by the conserved residues and is consistent with previously known biochemical data. This suggests that the IR family contains three FnIII domains in tandem in the extracellular juxtamembrane region.

【 授权许可】

Unknown