Structural Basis for the Distinct Membrane Binding Activity of the Homologous C2A Domains of Myoferlin and Dysferlin.

ABSTRACT: Dysferlin has been implicated in acute membrane repair processes, whereas myoferlin's activity is maximal during the myoblast fusion stage of early skeletal muscle cell development. Both proteins are similar in size and domain structure; however, despite the overall similarity, myoferlin's known physiological functions do not overlap with those of dysferlin. Here we present for the first time the X-ray crystal structure of human myoferlin C2A to 1.9 Å resolution bound to two divalent cations, and compare its three-dimensional structure and membrane binding activities to that of dysferlin C2A. We find that while dysferlin C2A binds membranes in a Ca²⁺-dependent manner, Ca²⁺ binding was the rate-limiting kinetic step for this interaction. Myoferlin C2A, on the other han

SUBMITTER: Harsini FM 

PROVIDER: S-EPMC6599597 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature