Structure of the ACF7 EF-Hand-GAR Module and Delineation of Microtubule Binding Determinants.

ABSTRACT: Spectraplakins are large molecules that cross-link F-actin and microtubules (MTs). Mutations in spectraplakins yield defective cell polarization, aberrant focal adhesion dynamics, and dystonia. We present the 2.8 Å crystal structure of the hACF7 EF1-EF2-GAR MT-binding module and delineate the GAR residues critical for MT binding. The EF1-EF2 and GAR domains are autonomous domains connected by a flexible linker. The EF1-EF2 domain is an EF?-scaffold with two bound Ca2+ ions that straddle an N-terminal ? helix. The GAR domain has a unique ?/? sandwich fold that coordinates Zn2+. While the EF1-EF2 domain is not sufficient for MT binding, the GAR domain is and likely enhances EF1-EF2-MT engagement. Residues in a conserved basic patch, distal to the GAR domain's Zn2+-binding site, mediate MT binding.

SUBMITTER: Lane TR 

PROVIDER: S-EPMC5920566 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature