Back to Search
Start Over
Structure of the ACF7 EF-Hand-GAR Module and Delineation of Microtubule Binding Determinants
- Publication Year :
- 2017
-
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 A 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.
- Subjects :
- 0301 basic medicine
Plasma protein binding
Biology
Bioinformatics
Microtubules
Article
Focal adhesion
03 medical and health sciences
0302 clinical medicine
Structural Biology
Microtubule
Cell polarity
Humans
EF Hand Motifs
Molecular Biology
Actin
Binding Sites
EF hand
Microfilament Proteins
Zinc
030104 developmental biology
HEK293 Cells
MACF1
Mutation
Biophysics
Linker
030217 neurology & neurosurgery
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....db2ecf88b3fc9b12c1d94036ee7e6224