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Molecular basis of the head-to-tail assembly of giant muscle proteins obscurin-like 1 and titin.

ABSTRACT: Large filament proteins in muscle sarcomeres comprise many immunoglobulin-like domains that provide a molecular platform for self-assembly and interactions with heterologous protein partners. We have unravelled the molecular basis for the head-to-tail interaction of the carboxyl terminus of titin and the amino-terminus of obscurin-like-1 by X-ray crystallography. The binary complex is formed by a parallel intermolecular beta-sheet that presents a novel immunoglobulin-like domain-mediated assembly mechanism in muscle filament proteins. Complementary binding data show that the assembly is entropy-driven rather than dominated data by specific polar interactions. The assembly observed leads to a V-shaped zipper-like arrangement of the two filament proteins.

SUBMITTER: Sauer F

PROVIDER: S-EPMC2897112 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Molecular basis of the head-to-tail assembly of giant muscle proteins obscurin-like 1 and titin.

Sauer Florian F Vahokoski Juha J Song Young-Hwa YH Wilmanns Matthias M

EMBO reports 20100521 7

Large filament proteins in muscle sarcomeres comprise many immunoglobulin-like domains that provide a molecular platform for self-assembly and interactions with heterologous protein partners. We have unravelled the molecular basis for the head-to-tail interaction of the carboxyl terminus of titin and the amino-terminus of obscurin-like-1 by X-ray crystallography. The binary complex is formed by a parallel intermolecular beta-sheet that presents a novel immunoglobulin-like domain-mediated assembl ...[more]

PMID: 20489725

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Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex.

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Downsizing the molecular spring of the giant protein titin reveals that skeletal muscle titin determines passive stiffness and drives longitudinal hypertrophy.

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Structure of giant muscle proteins.

Project description:Giant muscle proteins (e.g., titin, nebulin, and obscurin) play a seminal role in muscle elasticity, stretch response, and sarcomeric organization. Each giant protein consists of multiple tandem structural domains, usually arranged in a modular fashion spanning 500 kDa to 4 MDa. Although many of the domains are similar in structure, subtle differences create a unique function of each domain. Recent high and low resolution structural and dynamic studies now suggest more nuanced overall protein structures than previously realized. These findings show that atomic structure, interactions between tandem domains, and intrasarcomeric environment all influence the shape, motion, and therefore function of giant proteins. In this article we will review the current understanding of titin, obscurin, and nebulin structure, from the atomic level through the molecular level.

| S-EPMC3859903 | biostudies-literature

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