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Structure. 2017 Jul 5;25(7):1130-1138.e6. doi: 10.1016/j.str.2017.05.006. Epub 2017 Jun 8.

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

Author information

1
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA; Molecular and Cellular Biophysics Program, University of North Carolina, Chapel Hill, NC 27599, USA.
2
Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA; Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
3
Molecular and Cellular Biophysics Program, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: kslep@bio.unc.edu.

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 EFβ-scaffold with two bound Ca2+ ions that straddle an N-terminal α helix. The GAR domain has a unique α/β 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.

KEYWORDS:

ACF7; EF Hand; GAR; Gas2; MACF1; actin; microtubule; spectraplakin

PMID:
28602822
PMCID:
PMC5920566
DOI:
10.1016/j.str.2017.05.006
[Indexed for MEDLINE]
Free PMC Article

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