I型转化生长因子β受体胞质结构域与FKBP12复合物的晶体结构

Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12.

作者信息

Huse M, Chen Y G, Massagué J, Kuriyan J

机构信息

Laboratories of Molecular Biophysics, Rockefeller University, New York, New York 10021, USA.

出版信息

Cell. 1999 Feb 5;96(3):425-36. doi: 10.1016/s0092-8674(00)80555-3.

DOI:10.1016/s0092-8674(00)80555-3

PMID:10025408

Abstract

Activation of the type I TGFbeta receptor (TbetaR-I) requires phosphorylation of a regulatory segment known as the GS region, located upstream of the serine/threonine kinase domain in the cytoplasmic portion of the receptor. The crystal structure of a fragment of unphosphorylated TbetaR-I, containing both the GS region and the catalytic domain, has been determined in complex with the FK506-binding protein FKBP12. TbetaR-I adopts an inactive conformation that is maintained by the unphosphorylated GS region. FKBP12 binds to the GS region of the receptor, capping the TbetaR-II phosphorylation sites and further stabilizing the inactive conformation of TbetaR-I. Certain structural features at the catalytic center of TbetaR-I are characteristic of tyrosine kinases rather than Ser/Thr kinases.

摘要

I型转化生长因子β受体（TβR-I）的激活需要对一个称为GS区域的调节片段进行磷酸化，该区域位于受体细胞质部分丝氨酸/苏氨酸激酶结构域的上游。已确定未磷酸化的TβR-I片段（包含GS区域和催化结构域）与FK506结合蛋白FKBP12形成复合物的晶体结构。TβR-I呈现出一种由未磷酸化的GS区域维持的无活性构象。FKBP12与受体的GS区域结合，覆盖TβR-II磷酸化位点，并进一步稳定TβR-I的无活性构象。TβR-I催化中心的某些结构特征是酪氨酸激酶而非丝氨酸/苏氨酸激酶所特有的。