The Structure and Regulation of Human Muscle α-Actinin | Zendy

Euripedes de Almeida Ribeiro | Zendy; Nikos Pinotsis | Zendy; Andrea Ghisleni | Zendy; Anita Salmazo | Zendy; Petr V. Konarev | Zendy; Július Košťan | Zendy; Björn Sjöblom | Zendy; Claudia Schreiner | Zendy; Anton A. Polyansky | Zendy; Eirini A. Gkougkoulia | Zendy; Mark Holt | Zendy; Finn L. Aachmann | Zendy; Bojan Žagrović | Zendy; Enrica Bordig | Zendy; Katharina F. Pirker | Zendy; Dmitri I. Svergun | Zendy; Mathias Gautel | Zendy; Kristina DjinovićCarugo | Zendy

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The Structure and Regulation of Human Muscle α-Actinin

Author(s) -

Euripedes de Almeida Ribeiro,

Nikos Pinotsis,

Andrea Ghisleni,

Anita Salmazo,

Petr V. Konarev,

Július Košťan,

Björn Sjöblom,

Claudia Schreiner,

Anton A. Polyansky,

Eirini A. Gkougkoulia,

Mark Holt,

Finn L. Aachmann,

Bojan Žagrović,

Enrica Bordig,

Katharina F. Pirker,

Dmitri I. Svergun,

Mathias Gautel,

Kristina DjinovićCarugo

Publication year - 2014

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2014.10.056

Subject(s) - spectrin , mechanosensation , biology , titin , actinin , actin , microbiology and biotechnology , cytoskeleton , actin binding protein , epb41 , actin cytoskeleton , cell , myocyte , sarcomere , biochemistry , receptor , ion channel

The spectrin superfamily of proteins plays key roles in assembling the actin cytoskeleton in various cell types, crosslinks actin filaments, and acts as scaffolds for the assembly of large protein complexes involved in structural integrity and mechanosensation, as well as cell signaling. α-actinins in particular are the major actin crosslinkers in muscle Z-disks, focal adhesions, and actin stress fibers. We report a complete high-resolution structure of the 200 kDa α-actinin-2 dimer from striated muscle and explore its functional implications on the biochemical and cellular level. The structure provides insight into the phosphoinositide-based mechanism controlling its interaction with sarcomeric proteins such as titin, lays a foundation for studying the impact of pathogenic mutations at molecular resolution, and is likely to be broadly relevant for the regulation of spectrin-like proteins.

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