Structural basis for Rab23 activation and a loss-of-function mutation in Carpenter syndrome.

ABSTRACT: Rab23 is a member of the Rab family of small GTPases. It plays crucial roles in Hedgehog signaling, ciliary transport, and embryonic development. As a small GTPase, Rab23 cycles between the GDP-bound inactivated state and the GTP-bound activated state. Mutations in Rab23 are directly implicated in Carpenter syndrome, a development disorder characterized by deformed skulls, abnormal fingers or toes, and intellectual disabilities. Several clinical point mutations, for example, M12K, C85R, and Y79del, have been found to occur within the GTPase domain. However, the mechanisms of activation of Rab23 and pathogenesis of its clinical mutants are still unclear with limited structural information. So far, there are only two reported crystal structures of mouse Rab23 in complex with GDP. Here, we de

SUBMITTER: Chau YY 

PROVIDER: S-EPMC11730874 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature