1tnn

From Proteopedia

Revision as of 14:57, 15 February 2008

TERTIARY STRUCTURE OF AN IMMUNOGLOBULIN-LIKE DOMAIN FROM THE GIANT MUSCLE PROTEIN TITIN: A NEW MEMBER OF THE I SET

Overview

BACKGROUND: Titin is a gigantic protein located in the thick filament of, vertebrate muscles. The putative functions of titin range from, interactions with myosin and other muscle proteins to a role in muscle, recoil. Analysis of its complete sequence has shown that titin is a, multi-domain protein containing several copies of modules of 100 amino, acids each. These are thought to belong to the fibronectin type-III and, immunoglobulin superfamilies. So far, a complete structural determination, has not been carried out on any of the titin modules. RESULTS: The, three-dimensional structure of an immunoglobulin module, located in the, M-line of the sarcomere close to the titin C terminus and called 'M5', was, determined by multi-dimensional NMR spectroscopy. The structure has the, predicted immunoglobulin fold with two beta-sheets packed against each, other. Each sheet contains four strands. The structure of M5 belongs to, the I (intermediate) set of the immunoglobulin superfamily and is very, similar to telokin, which is also found in muscles. Although M5 and, telokin have relatively little sequence similarity, the two proteins, clearly share the same hydrophobic core. The major difference between, telokin and the titin M5 module is the absence of the C' strand in the, latter. CONCLUSIONS: The titin domains and several of the, immunoglobulin-like domains from other modular muscle proteins are highly, conserved at the positions corresponding to the hydrophobic core of M5., Our results indicate that it may be possible to use the structure of M5 as, a molecular template to model most of the other immunoglobulin-like, domains in muscle titin.

Disease

Known diseases associated with this structure: Cardiomyopathy, dilated, 1G OMIM:[188840], Cardiomyopathy, familial hypertrophic OMIM:[188840], Muscular dystrophy, limb-girdle, type 2J OMIM:[188840], Myopathy, early-onset, with fatal cardiomyopathy OMIM:[188840], Myopathy, proximal, with early respiratory muscle involvement OMIM:[188840], Tibial muscular dystrophy, tardive OMIM:[188840]

About this Structure

1TNN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Tertiary structure of an immunoglobulin-like domain from the giant muscle protein titin: a new member of the I set., Pfuhl M, Pastore A, Structure. 1995 Apr 15;3(4):391-401. PMID:7613868

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