Journal
SCIENCE ADVANCES
Volume 5, Issue 10, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aax8855
Keywords
-
Categories
Funding
- NIH [CA221289, HL122416, HL071818, S10OD020011]
- Walther Cancer Foundation
Ask authors/readers for more resources
PIP3-dependent Rac exchanger 1 (P-Rex1) is activated downstream of G protein-coupled receptors to promote neutrophil migration and metastasis. The structure of more than half of the enzyme and its regulatory G protein binding site are unknown. Our 3.2 angstrom cryo-EM structure of the P-Rex1-G beta gamma, complex reveals that the carboxyl-terminal half of P-Rex1 adopts a complex fold most similar to those of Legionella phosphoinositide phosphatases. Although catalytically inert, the domain coalesces with a DEP domain and two PDZ domains to form an extensive docking site for Gk. Hydrogen-deuterium exchange mass spectrometry suggests that G beta gamma, binding induces allosteric changes in P-Rex1, but functional assays indicate that membrane localization is also required for full activation. Thus, a multidomain assembly is key to the regulation of P-Rex1 by G beta gamma, and the formation of a membrane-localized scaffold optimized for recruitment of other signaling proteins such as PKA and PTEN.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available