Palindromic assembly of the giant muscle protein titin in the sarcomeric Z-disk

Zou, P.; Wilmanns, M.; Popov, A.; Pinotsis, N.; Mayans, O. M.; Gautel, M.; Mavridis, I.; Lange, S.; Song, Y. H.

doi:10.1038/nature04343

Journal Article

Palindromic assembly of the giant muscle protein titin in the sarcomeric Z-disk

Zou, P. ; Pinotsis, N. ; Lange, S. ; Song, Y. H. ; Popov, A. ; Mavridis, I. ; Mayans, O. M. ; Gautel, M. ; Wilmanns, M. ; DESY

2006
Nature Publising Group London [u.a.]

Nature <London> 439, 233 (2006) [10.1038/nature04343]

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Please use a persistent id in citations: doi:10.1038/nature04343

Abstract: The Z-disk of striated and cardiac muscle sarcomeres is one of the most densely packed cellular structures in eukaryotic cells. It provides the architectural framework for assembling and anchoring the largest known muscle filament systems by an extensive network of protein-protein interactions, requiring an extraordinary level of mechanical stability. Here we show, using X-ray crystallography, how the amino terminus of the longest filament component, the giant muscle protein titin, is assembled into an antiparallel (2:1) sandwich complex by the Z-disk ligand telethonin. The pseudosymmetric structure of telethonin mediates a unique palindromic arrangement of two titin filaments, a type of molecular assembly previously found only in protein-DNA complexes. We have confirmed its unique architecture in vivo by protein complementation assays, and in vitro by experiments using fluorescence resonance energy transfer. The model proposed may provide a molecular paradigm of how major sarcomeric filaments are crosslinked, anchored and aligned within complex cytoskeletal networks.

Keyword(s): Amino Acid Sequence (MeSH) ; Animals (MeSH) ; Animals, Newborn (MeSH) ; Crystallography, X-Ray (MeSH) ; Fluorescence Resonance Energy Transfer (MeSH) ; Genetic Complementation Test (MeSH) ; Hydrogen Bonding (MeSH) ; Ligands (MeSH) ; Models, Molecular (MeSH) ; Molecular Sequence Data (MeSH) ; Multiprotein Complexes: chemistry (MeSH) ; Multiprotein Complexes: metabolism (MeSH) ; Muscle Proteins: chemistry (MeSH) ; Muscle Proteins: genetics (MeSH) ; Muscle Proteins: metabolism (MeSH) ; Myocytes, Cardiac: chemistry (MeSH) ; Myocytes, Cardiac: metabolism (MeSH) ; Protein Binding (MeSH) ; Protein Conformation (MeSH) ; Protein Kinases: chemistry (MeSH) ; Protein Kinases: genetics (MeSH) ; Protein Kinases: metabolism (MeSH) ; Rats (MeSH) ; Sarcomeres: chemistry (MeSH) ; Sarcomeres: metabolism (MeSH) ; Ligands ; Multiprotein Complexes ; Muscle Proteins ; connectin ; telethonin protein, rat ; Protein Kinases