Obscurin, a giant sarcomeric Rho guanine nucleotide exchange factor protein involved in sarcomere assembly.
Vertebrate-striated muscle is assumed to owe its remarkable order to the molecular ruler functions of the giant modular signaling proteins, titin and nebulin. It was believed that these two proteins represented unique results of protein evolution in vertebrate muscle. In this paper we report the identification of a third giant protein from vertebrate muscle, obscurin, encoded on chromosome 1q42. Obscurin is approximately 800 kD and is expressed specifically in skeletal and cardiac muscle. The complete cDNA sequence of obscurin reveals a modular architecture, consisting of >67 intracellular immunoglobulin (Ig)- or fibronectin-3-like domains with multiple splice variants. A large region of obscurin shows a modular architecture of tandem Ig domains reminiscent of the elastic region of titin. The COOH-terminal region of obscurin interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin. Both proteins coassemble during myofibrillogenesis. During the progression of myofibrillogenesis, all obscurin epitopes become detectable at the M band. The presence of a calmodulin-binding IQ motif, and a Rho guanine nucleotide exchange factor domain in the COOH-terminal region suggest that obscurin is involved in Ca(2+)/calmodulin, as well as G protein-coupled signal transduction in the sarcomere.
Young
P
P
European Molecular Biology Laboratory, Structural Biology Division, 69117 Heidelberg, Germany.
Ehler
E
E
Gautel
M
M
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002147:Calmodulin / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D002642:Chick Embryo; D002878:Chromosomes, Human, Pair 1; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D000939:Epitopes; D015723:Gene Library; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D018613:Microscopy, Confocal; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D064067:Rho Guanine Nucleotide Exchange Factors; D012518:Sarcomeres / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D014162:Transfection; D020741:rho GTP-Binding Proteins / Q000737:chemistry* / Q000502:physiology*
D002147:Calmodulin; D018076:DNA, Complementary; D000939:Epitopes; D020662:Guanine Nucleotide Exchange Factors; D007136:Immunoglobulins; D009124:Muscle Proteins; C503780:Obscn protein, rat; D064067:Rho Guanine Nucleotide Exchange Factors; C578224:OBSCN protein, human; D017346:Protein Serine-Threonine Kinases; D020741:rho GTP-Binding Proteins