Molecular basis of the head-to-tail assembly of giant muscle proteins obscurin-like 1 and titin.
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.
Sauer
Florian
F
EMBL-Hamburg, Notkestrasse 85, Hamburg D-22603, Germany.
Vahokoski
Juha
J
Song
Young-Hwa
YH
Wilmanns
Matthias
M
D000595:Amino Acid Sequence; D064211:Connectin; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
D064211:Connectin; D003598:Cytoskeletal Proteins; D009124:Muscle Proteins; C522000:OBSL1 protein, human; C577285:TTN protein, human; D011494:Protein Kinases