5A36

Mutations in the Calponin homology domain of Alpha-Actinin-2 affect Actin binding and incorporation in muscle.

Summary for 5A36

• Entry DOI: 10.2210/pdb5a36/pdb
• Related: 5A37 5A38
• Descriptor: ALPHA-ACTININ-2 (2 entities in total)
• Functional Keywords: structural protein
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm, myofibril, sarcomere, Z line : P35609
• Total number of polymer chains: 2
• Total formula weight: 57173.77

Authors

Haywood, N.J.,Wolny, M.,Trinh, C.H.,Shuping, Y.,Edwards, T.A.,Peckham, M. (deposition date: 2015-05-27, release date: 2016-06-22, Last modification date: 2024-05-08)

Primary citation

Haywood, N.,Wolny, M.,Rogers, B.,Trinh, C.H.,Shuping, Y.,Edwards, T.A.,Peckham, M.
Hypertrophic Cardiomyopathy Mutations in the Calponin-Homology Domain of Actn2 Affect Actin Binding and Cardiomyocyte Z-Disc Incorporation.
Biochem.J., 473:2485-, 2016

PubMed Abstract: α-Actinin-2 (ACTN2) is the only muscle isoform of α-actinin expressed in cardiac muscle. Mutations in this protein have been implicated in mild to moderate forms of hypertrophic cardiomyopathy (HCM). We have investigated the effects of two mutations identified from HCM patients, A119T and G111V, on the secondary and tertiary structure of a purified actin binding domain (ABD) of ACTN2 by circular dichroism and X-ray crystallography, and show small but distinct changes for both mutations. We also find that both mutants have reduced F-actin binding affinity, although the differences are not significant. The full length mEos2 tagged protein expressed in adult cardiomyocytes shows that both mutations additionally affect Z-disc localization and dynamic behaviour. Overall, these two mutations have small effects on structure, function and behaviour, which may contribute to a mild phenotype for this disease.

PubMed: 27287556
DOI: 10.1042/BCJ20160421

Experimental method

X-RAY DIFFRACTION (2 Å)