Open AccessA Molecular Map of the Interactions between Titin and Myosin‐Binding Protein C
Author(s) -
Freiburg Alexandra,
Gautel Mathias
Publication year - 1996
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1996.00317.x
Subject(s) - titin , obscurin , sarcomere , myosin , immunoglobulin domain , biology , myosin head , microbiology and biotechnology , protein filament , chemistry , biophysics , myosin light chain kinase , genetics , myocyte , antibody
The thick filaments of vertebrate striated muscles contain with myosin a number of accessory proteins of the intracellular immunoglobulin superfamily, which are localized in a distinct pattern of stripes 43 nm apart. The specific localization of these proteins is believed to be due partly to their interaction with the giant muscle protein titin (also called connectin), which spans the entire sarcomere and may act as a molecular ruler. We have used recombinant fragments of titin covering the thick filament region to investigate their interaction with myosin‐binding protein C (MyBP‐C) from skeletal and cardiac muscle. The interaction of titin and MyBP‐C is directed by a subset of titin immunoglobulin domains that are specific for the C‐region of the thick filament, supporting the ruler hypothesis for the myosin‐binding proteins. The interaction of recombinant titin with overlapping fragments of human cardiac MyBP‐C maps the titin‐binding site within the C‐terminal region, which is deleted in patients suffering from the chromosome‐11–associated form of familial hypertrophic cardiomyopathy. This disorder is therefore likely to be the result of thick‐filament misassembly by abolishing the ternary interaction of titin, myosin and MyBP‐C.