The Structure and Regulation of Human Muscle α-Actinin

Euripedes de Almeida Ribeiro; Nikos Pinotsis; Andrea Ghisleni; Anita Salmazo; Petr V Konarev; Julius Kostan; Björn Sjöblom; Claudia Schreiner; Anton A Polyansky; Eirini A Gkougkoulia; Mark R Holt; Finn L Aachmann; Bojan Zagrović; Enrica Bordignon; Katharina F Pirker; Dmitri I Svergun; Mathias Gautel; Kristina Djinović-Carugo

doi:10.1016/j.cell.2014.10.056

The Structure and Regulation of Human Muscle α-Actinin

Euripedes de Almeida Ribeiro, Nikos Pinotsis, Andrea Ghisleni, Anita Salmazo, Petr V Konarev, Julius Kostan, Björn Sjöblom, Claudia Schreiner, Anton A Polyansky, Eirini A Gkougkoulia, Mark R Holt, Finn L Aachmann, Bojan Zagrović, Enrica Bordignon, Katharina F Pirker, Dmitri I Svergun, Mathias Gautel, Kristina Djinović-Carugo

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Abstract

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.

Original language	English
Pages (from-to)	1447-1460
Number of pages	14
Journal	Cell
Volume	159
Issue number	6
Early online date	26 Nov 2014
DOIs	https://doi.org/10.1016/j.cell.2014.10.056
Publication status	Published - 4 Dec 2014

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The Structure and Regulation_RIBEIROJR_Accepted24Oct2014_GOLD VoRFinal published version, 4.79 MBLicence: CC BY

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Ribeiro, E. D. A., Pinotsis, N., Ghisleni, A., Salmazo, A., Konarev, P. V., Kostan, J., Sjöblom, B., Schreiner, C., Polyansky, A. A., Gkougkoulia, E. A., Holt, M. R., Aachmann, F. L., Zagrović, B., Bordignon, E., Pirker, K. F., Svergun, D. I., Gautel, M., & Djinović-Carugo, K. (2014). The Structure and Regulation of Human Muscle α-Actinin. Cell, 159(6), 1447-1460. https://doi.org/10.1016/j.cell.2014.10.056

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title = "The Structure and Regulation of Human Muscle α-Actinin",

abstract = "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.",

author = "Ribeiro, {Euripedes de Almeida} and Nikos Pinotsis and Andrea Ghisleni and Anita Salmazo and Konarev, {Petr V} and Julius Kostan and Bj{\"o}rn Sj{\"o}blom and Claudia Schreiner and Polyansky, {Anton A} and Gkougkoulia, {Eirini A} and Holt, {Mark R} and Aachmann, {Finn L} and Bojan Zagrovi{\'c} and Enrica Bordignon and Pirker, {Katharina F} and Svergun, {Dmitri I} and Mathias Gautel and Kristina Djinovi{\'c}-Carugo",

year = "2014",

month = dec,

day = "4",

doi = "10.1016/j.cell.2014.10.056",

language = "English",

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Ribeiro, EDA, Pinotsis, N, Ghisleni, A, Salmazo, A, Konarev, PV, Kostan, J, Sjöblom, B, Schreiner, C, Polyansky, AA, Gkougkoulia, EA, Holt, MR, Aachmann, FL, Zagrović, B, Bordignon, E, Pirker, KF, Svergun, DI, Gautel, M & Djinović-Carugo, K 2014, 'The Structure and Regulation of Human Muscle α-Actinin', Cell, vol. 159, no. 6, pp. 1447-1460. https://doi.org/10.1016/j.cell.2014.10.056

TY - JOUR

T1 - The Structure and Regulation of Human Muscle α-Actinin

AU - Ribeiro, Euripedes de Almeida

AU - Pinotsis, Nikos

AU - Ghisleni, Andrea

AU - Salmazo, Anita

AU - Konarev, Petr V

AU - Kostan, Julius

AU - Sjöblom, Björn

AU - Schreiner, Claudia

AU - Polyansky, Anton A

AU - Gkougkoulia, Eirini A

AU - Holt, Mark R

AU - Aachmann, Finn L

AU - Zagrović, Bojan

AU - Bordignon, Enrica

AU - Pirker, Katharina F

AU - Svergun, Dmitri I

AU - Gautel, Mathias

AU - Djinović-Carugo, Kristina

PY - 2014/12/4

Y1 - 2014/12/4

N2 - 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.

AB - 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.

U2 - 10.1016/j.cell.2014.10.056

DO - 10.1016/j.cell.2014.10.056

M3 - Article

C2 - 25433700

SN - 0092-8674

VL - 159

SP - 1447

EP - 1460

JO - Cell

JF - Cell

IS - 6

ER -

The Structure and Regulation of Human Muscle α-Actinin

Abstract

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