Crystal structure of the rigor-like human non-muscle myosin-2 motor domain

Stefan Münnich; Salma Pathan-Chhatbar; Dietmar J Manstein

doi:10.1016/j.febslet.2014.11.007

Crystal structure of the rigor-like human non-muscle myosin-2 motor domain

FEBS Lett. 2014 Dec 20;588(24):4754-60. doi: 10.1016/j.febslet.2014.11.007. Epub 2014 Nov 15.

Authors

Stefan Münnich¹, Salma Pathan-Chhatbar¹, Dietmar J Manstein²

Affiliations

¹ Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany.
² Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany. Electronic address: manstein.dietmar@mh-hannover.de.

PMID: 25451231
DOI: 10.1016/j.febslet.2014.11.007

Abstract

We determined the crystal structure of the motor domain of human non-muscle myosin 2B (NM-2B) in a nucleotide-free state and at a resolution of 2.8 Å. The structure shows the motor domain with an open active site and the large cleft that divides the 50 kDa domain in a closed state. Compared to other rigor-like myosin motor domain structures, our structure shows subtle but significant conformational changes in regions important for actin binding and mechanochemical coupling. Moreover, our crystal structure helps to rationalize the impact of myosin, heavy chain 9 (MYH9)-related disease mutations Arg709Cys and Arg709His on the kinetic and functional properties of NM-2B and of the closely related non-muscle myosin 2A (NM-2A).

Keywords: MYH9-related disease; Myosin; NM-2B; Non-muscle myosin-2B; X-ray crystallography.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Cloning, Molecular
Crystallography, X-Ray
Humans
Models, Molecular
Mutation
Myosins / chemistry*
Myosins / genetics
Myosins / isolation & purification
Protein Structure, Tertiary

Substances

Myosins

Associated data

PDB/4PD3