Solution structure of the first immunoglobulin domain of human myotilin.
Myotilin is a 57 kDa actin-binding and -bundling protein that consists of a unique serine-rich amino-terminus, two Ig-domains and a short carboxy-terminus with a PDZ-binding motif. Myotilin localizes in sarcomeric Z-discs, where it interacts with several sarcomeric proteins. Point mutations in myotilin cause muscle disorders morphologically highlighted by sarcomeric disarray and aggregation. The actin-binding and dimerization propensity of myotilin has been mapped to the Ig-domains. Here we present high-resolution structure of the first Ig-domain of myotilin (MyoIg1) determined with solution state NMR spectroscopy. Nearly complete chemical shift assignments of MyoIg1 were achieved despite several missing backbone 1H-15N-HSQC signals. The structure derived from distance and dihedral angle restraints using torsion angle dynamics was further refined using molecular dynamics. The structure of MyoIg1 exhibits I-type Ig-fold. The absence of several backbone 1H-15N-HSQC signals can be explained by conformational exchange taking place at the hydrophobic core of the protein.
Laboratory of Organic Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55, 00014 Helsinki, Finland. Outi.K.Heikkinen@helsinki.fi
Outi
O
Heikkinen
Perttu
P
Permi
Harri
H
Koskela
Olli
O
Carpén
Jari
J
Ylänne
Ilkka
I
Kilpeläinen
D064211:Connectin; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D008840:Microfilament Proteins / Q000737:chemistry; D008958:Models, Molecular; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry
D064211:Connectin; D003598:Cytoskeletal Proteins; D007136:Immunoglobulins; C577290:MYOT protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins; D011994:Recombinant Proteins