Point mutations alter the mechanical stability of immunoglobulin modules

H Li; M Carrion-Vazquez; A F Oberhauser; P E Marszalek; J M Fernandez

doi:10.1038/81964

Point mutations alter the mechanical stability of immunoglobulin modules

Nat Struct Biol. 2000 Dec;7(12):1117-20. doi: 10.1038/81964.

Authors

H Li¹, M Carrion-Vazquez, A F Oberhauser, P E Marszalek, J M Fernandez

Affiliation

¹ Department of Physiology and Biophysics, Mayo Foundation, Rochester, Minnesota 55905, USA.

PMID: 11101892
DOI: 10.1038/81964

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Substitution / genetics
Connectin
Humans
Immunoglobulins / chemistry*
Kinetics
Microscopy, Atomic Force
Models, Molecular
Monte Carlo Method
Muscle Proteins / chemistry*
Muscle Proteins / genetics
Muscle Proteins / metabolism*
Myocardium / chemistry
Phenotype
Point Mutation / genetics*
Proline / genetics
Proline / metabolism
Protein Denaturation
Protein Folding*
Protein Kinases / chemistry*
Protein Kinases / genetics
Protein Kinases / metabolism*
Protein Renaturation
Protein Structure, Secondary
Protein Structure, Tertiary
Thermodynamics

Substances

Connectin
Immunoglobulins
Muscle Proteins
TTN protein, human
Proline
Protein Kinases