Unknown

Dataset Information

0

Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases.


ABSTRACT: Stem cell factor (SCF) binds to and activates the KIT receptor, a class III receptor tyrosine kinase (RTK), to stimulate diverse processes including melanogenesis, gametogenesis and hematopoeisis. Dysregulation of KIT activation is associated with many cancers. We report a 2.5 A crystal structure of the functional core of SCF bound to the extracellular ligand-binding domains of KIT. The structure reveals a 'wrapping' SCF-recognition mode by KIT, in which KIT adopts a bent conformation to facilitate each of its first three immunoglobulin (Ig)-like domains to interact with SCF. Three surface epitopes on SCF, an extended loop, the B and C helices, and the N-terminal segment, contact distinct KIT domains, with two of the epitopes undergoing large conformational changes upon receptor binding. The SCF/KIT complex reveals a unique RTK dimerization assembly, and a novel recognition mode between four-helix bundle cytokines and Ig-family receptors. It serves as a framework for understanding the activation mechanisms of class III RTKs.

SUBMITTER: Liu H 

PROVIDER: S-EPMC1794399 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases.

Liu Heli H   Chen Xiaoyan X   Focia Pamela J PJ   He Xiaolin X  

The EMBO journal 20070125 3


Stem cell factor (SCF) binds to and activates the KIT receptor, a class III receptor tyrosine kinase (RTK), to stimulate diverse processes including melanogenesis, gametogenesis and hematopoeisis. Dysregulation of KIT activation is associated with many cancers. We report a 2.5 A crystal structure of the functional core of SCF bound to the extracellular ligand-binding domains of KIT. The structure reveals a 'wrapping' SCF-recognition mode by KIT, in which KIT adopts a bent conformation to facilit  ...[more]

Similar Datasets

| S-EPMC2587541 | biostudies-literature
| S-EPMC3020666 | biostudies-literature
| S-EPMC5192866 | biostudies-literature
| S-EPMC3816449 | biostudies-literature
| S-EPMC5507626 | biostudies-literature
| S-EPMC2826351 | biostudies-literature
| S-EPMC3509443 | biostudies-literature
| S-EPMC6300111 | biostudies-literature
| S-EPMC6940998 | biostudies-literature
| S-EPMC6964135 | biostudies-literature