5A37

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

5A37 の概要

• エントリーDOI: 10.2210/pdb5a37/pdb
• 関連するPDBエントリー: 5A36 5A38
• 分子名称: HUMAN ALPHA-ACTININ-2 (2 entities in total)
• 機能のキーワード: actin-binding protein, human alpha-actinin-2, calponin homology domains
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm, myofibril, sarcomere, Z line : P35609
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57257.94

構造登録者

Haywood, N.J.,Wolny, M.,Trinh, C.H.,Shuping, Y.,Edwards, T.A.,Peckham, M. (登録日: 2015-05-27, 公開日: 2016-06-22, 最終更新日: 2024-05-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.88 Å)