Mechanical dissociation of the M‐band titin/obscurin complex is directionally dependent. Issue 15 (19th May 2015)

• Record Type: Journal Article
• Authors: Caldwell, Tracy A.; Sumner, Isaiah; Wright, Nathan T.
• Is Part Of: FEBS letters. Volume 589:Issue 15(2015)
• Page Start: 1735
• Page End: 1739
• Publication Date: 2015-05-19
• Subjects: M10 -- Steered molecular dynamic -- Shearing -- Peeling -- Muscular dystrophy; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2015.05.023
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Titin and obscurin, two giant muscle proteins, bind to each other in an antiparallel Ig–Ig fashion at the M‐band. This interaction must be able to withstand the mechanical strain that the M‐band typically experiences and remain intact. The mechanical force on these domains is likely exerted along one of two axes: a longitudinal axis, resulting in a 'shearing' force, or a lateral axis, resulting in a 'peeling' force. Here we present molecular dynamics data suggesting that these forces result in distinct unraveling pathways of the titin/obscurin complex and that peeling the domains apart requires less work and force. Abstract : We modeled how mechanical force influences the titin/obscurin protein complex. When sheared apart, the titin/obscurin complex unravels by slipping past its neighbor. When peeled apart, the complex unravels by rotating and forming a long‐lived stable intermediate. Due to forming fewer transient hydrogen bonds, the peeling model requires both less force and less overall work.