蛋白质酪氨酸磷酸酶
信号转导衔接蛋白
二聚体
磷酸酶
化学
同源(生物学)
生物
遗传学
细胞生物学
酪氨酸
生物化学
信号转导
基因
磷酸化
有机化学
作者
José A. Manso,T. Kuroki Marcos,Virginia Ruiz-Martín,Javier Casas,Pablo Alcón,Mariano Sánchez Crespo,Yolanda Bayón,José M. de Pereda,Andrés Alonso
标识
DOI:10.1007/s00018-022-04173-w
摘要
Mutations in the adaptor protein PSTPIP1 cause a spectrum of autoinflammatory diseases, including PAPA and PAMI; however, the mechanism underlying these diseases remains unknown. Most of these mutations lie in PSTPIP1 F-BAR domain, which binds to LYP, a protein tyrosine phosphatase associated with arthritis and lupus. To shed light on the mechanism by which these mutations generate autoinflammatory disorders, we solved the structure of the F-BAR domain of PSTPIP1 alone and bound to the C-terminal homology segment of LYP, revealing a novel mechanism of recognition of Pro-rich motifs by proteins in which a single LYP molecule binds to the PSTPIP1 F-BAR dimer. The residues R228, D246, E250, and E257 of PSTPIP1 that are mutated in immunological diseases directly interact with LYP. These findings link the disruption of the PSTPIP1/LYP interaction to these diseases, and support a critical role for LYP phosphatase in their pathogenesis.
科研通智能强力驱动
Strongly Powered by AbleSci AI