PDBsum entry 5a36

Structural protein

PDB id: 5a36

Contents

Protein chains

239 a.a.

224 a.a.

Waters ×117

PDB id:

5a36

Name:

Structural protein

Title:

Mutations in the calponin homology domain of alpha-actinin-2 affect actin binding and incorporation in muscle.

Structure:

Alpha-actinin-2. Chain: a, b. Fragment: calponin homology domain, unp residues 19-266. Synonym: alpha-actinin skeletal muscle isoform 2, f-actin cross- linking protein, human alpha-actinin-2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.00Å R-factor: 0.220 R-free: 0.269

Authors:

N.J.Haywood,M.Wolny,C.H.Trinh,Y.Shuping,T.A.Edwards,M.Peckham

Key ref:

N.J.Haywood et al. (2016). Hypertrophic cardiomyopathy mutations in the calponin-homology domain of ACTN2 affect actin binding and cardiomyocyte Z-disc incorporation. Biochem J, 473, 2485-2493. PubMed id: 27287556 DOI: 10.1042/BCJ20160421

Date:

27-May-15 Release date: 22-Jun-16

Protein chain

P35609  (ACTN2_HUMAN) -  Alpha-actinin-2 from Homo sapiens

Seq: 894 a.a.

Struc: 239 a.a.

Protein chain

P35609  (ACTN2_HUMAN) -  Alpha-actinin-2 from Homo sapiens

Seq: 894 a.a.

Struc: 224 a.a.

DOI no: 10.1042/BCJ20160421

Biochem J 473:2485-2493 (2016)

PubMed id: 27287556

Hypertrophic cardiomyopathy mutations in the calponin-homology domain of ACTN2 affect actin binding and cardiomyocyte Z-disc incorporation.

N.J.Haywood, M.Wolny, B.Rogers, C.H.Trinh, Y.Shuping, T.A.Edwards, M.Peckham.

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.