title: Point mutations alter the mechanical stability of immunoglobulin modules.
abstract: Immunoglobulin-like modules are common components of proteins that play mechanical roles in cells such as muscle elasticity and cell adhesion. Mutations in these proteins may affect their mechanical stability and thus may compromise their function. Using single molecule atomic force microscopy (AFM) and protein engineering, we demonstrate that point mutations in two beta-strands of an immunoglobulin module in human cardiac titin alter the mechanical stability of the protein, resulting in mechanical phenotypes. Our results demonstrate a previously unrecognized class of phenotypes that may be common in cell adhesion and muscle proteins.
authors: Department of Physiology and Biophysics, Mayo Foundation, Rochester, Minnesota 55905, USA.
authors: H
authors: H
authors: Li
authors: M
authors: M
authors: Carrion-Vazquez
authors: A F
authors: AF
authors: Oberhauser
authors: P E
authors: PE
authors: Marszalek
authors: J M
authors: JM
authors: Fernandez
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D064211:Connectin; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D007700:Kinetics; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D009010:Monte Carlo Method; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D011392:Proline / Q000235:genetics / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020673:Protein Renaturation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D064211:Connectin; D007136:Immunoglobulins; D009124:Muscle Proteins; C577285:TTN protein, human; D011392:Proline; D011494:Protein Kinases