title: Structure and stability of an immunoglobulin superfamily domain from twitchin, a muscle protein of the nematode Caenorhabditis elegans.
abstract: The NMR solution structure of an immunoglobulin superfamily module of twitchin (Ig 18') has been determined and the kinetic and equilibrium folding behaviour characterised. Thirty molecular coordinates were calculated using a hybrid distance geometry-simulated annealing protocol based on 1207 distance and 48 dihedral restraints. The atomic rms distributions about the mean coordinate for the ensemble of structures is 0.55( +/- 0.09) A for backbone atoms and 1.10( +/- 0.08) A for all heavy atoms. The protein has a topology very similar to that of telokin and the titin Ig domains and thus it falls into the I set of the immunoglobulin superfamily. The close agreement between the predicted and observed structures of Ig 18' demonstrates clearly that the I set profile can be applied in the structure prediction of immunoglobulin-like domains of diverse modular proteins. Folding studies reveal that the protein has relatively low thermodynamic stability, deltaG(H2O)U-F = 4.0 kcal mol(-1) at physiological pH. Unfolding studies suggest that the protein has considerable kinetic stability, the half life of the unfolding is greater than 40 minutes in the absence of denaturant.
authors.affiliation: Centre for Protein Engineering, MRC Unit of Protein Folding and Design, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Fong
authors.forename: S J
authors.initials: SJ
authors.lastname: Hamill
authors.forename: M
authors.initials: M
authors.lastname: Proctor
authors.forename: S M
authors.initials: SM
authors.lastname: Freund
authors.forename: G M
authors.initials: GM
authors.lastname: Benian
authors.forename: C
authors.initials: C
authors.lastname: Chothia
authors.forename: M
authors.initials: M
authors.lastname: Bycroft
authors.forename: J
authors.initials: J
authors.lastname: Clarke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry*; D029742:Caenorhabditis elegans Proteins; D002148:Calmodulin-Binding Proteins / Q000737:chemistry*; D015801:Helminth Proteins / Q000737:chemistry*; D007136:Immunoglobulins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry*; D009219:Myosin-Light-Chain Kinase; D010446:Peptide Fragments; D010455:Peptides; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D029742:Caenorhabditis elegans Proteins; D002148:Calmodulin-Binding Proteins; D015801:Helminth Proteins; D007136:Immunoglobulins; D009124:Muscle Proteins; D010446:Peptide Fragments; D010455:Peptides; C489233:unc-22 protein, C elegans; C060640:telokin; D009219:Myosin-Light-Chain Kinase