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.
Heikkinen
Outi
O
Laboratory of Organic Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55, 00014 Helsinki, Finland. Outi.K.Heikkinen@helsinki.fi
Permi
Perttu
P
Koskela
Harri
H
Carpén
Olli
O
Ylänne
Jari
J
Kilpeläinen
Ilkka
I
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