Solution structure of the first immunoglobulin domain of human myotilin

J Biomol NMR. 2009 Jun;44(2):107-12. doi: 10.1007/s10858-009-9320-4. Epub 2009 May 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Connectin
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / genetics
  • Escherichia coli / genetics
  • Humans
  • Immunoglobulins / chemistry*
  • Microfilament Proteins / chemistry
  • Models, Molecular
  • Muscle Proteins / chemistry*
  • Muscle Proteins / genetics
  • Nuclear Magnetic Resonance, Biomolecular*
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry

Substances

  • Connectin
  • Cytoskeletal Proteins
  • Immunoglobulins
  • MYOT protein, human
  • Microfilament Proteins
  • Muscle Proteins
  • Recombinant Proteins