Mechanical Unfolding of a Titin Ig Domain: Structure of Transition State Revealed by Combining Atomic Force Microscopy, Protein Engineering and Molecular Dynamics Simulations

• Published in: Journal of molecular biology Vol. 330; no. 4; pp. 867 - 877
• Main Authors: Best, Robert B., Fowler, Susan B., Toca Herrera, José L., Steward, Annette, Paci, Emanuele, Clarke, Jane
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 18.07.2003
• Subjects: AFM; Computer Simulation; Connectin; immunoglobulin; Immunoglobulins - chemistry; Microscopy, Atomic Force; Models, Molecular; muscle; Muscle Proteins - chemistry; Muscles - metabolism; Mutation; Protein Denaturation; Protein Folding; Protein Kinases - chemistry; Protein Structure, Tertiary; Proteins - chemistry; Thermodynamics; titin; titin; MD, molecular dynamics; immunoglobulin; Ig, immunoglobulin; TI I27, the 27th Ig-like domain from the I band of human cardiac titin; muscle; AFM; protein folding; AFM, atomic force microscopy; f and ‡ o, the transition states investigated by force and denaturant unfolding, respectively
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/S0022-2836(03)00618-1

Titin I27 shows a high resistance to unfolding when subject to external force. To investigate the molecular basis of this mechanical stability, protein engineering Φ-value analysis has been combined with atomic force microscopy to investigate the structure of the barrier to forced unfolding. The res...