Mechanistic Differences of Activation of Rac1^P29S and Rac1^A159V.

ABSTRACT: Rac1 is a small GTPase that plays key roles in actin reorganization, cell motility, and cell survival/growth as well as in various cancer types and neurodegenerative diseases. Similar to other Ras superfamily GTPases, Rac1 switches between active GTP-bound and inactive GDP-bound states. Switch I and II regions open and close during GDP/GTP exchange. P29S and A159V (paralogous to K-Ras^A146) mutations are the two most common somatic mutations of Rac1. Rac1^P29S is a known hotspot for melanoma, whereas Rac1^A159V most commonly occurs in head and neck cancer. To investigate how these substitutions induce the Rac1 dynamics, we used atomistic molecular dynamics simulations on the wild-type Rac1 and two mutant systems (P29S and A159V) in the GTP bound state, and on

SUBMITTER: Senyuz S 

PROVIDER: S-EPMC8154616 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature