Journal article
Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds
Proceedings of the National Academy of Sciences - PNAS, Vol.110(13), pp.5022-5027
03/26/2013
DOI: 10.1073/pnas.1218407110
PMCID: PMC3612643
PMID: 23460697
Abstract
As a key element in the cytoskeleton, actin filaments are highly dynamic structures that constantly sustain forces. However, the fundamental question of how force regulates actin dynamics is unclear. Using atomic force microscopy force-clamp experiments, we show that tensile force regulates G-actin/G-actin and G-actin/F-actin dissociation kinetics by prolonging bond lifetimes (catch bonds) at a low force range and by shortening bond lifetimes (slip bonds) beyond a threshold. Steered molecular dynamics simulations reveal force-induced formation of new interactions that include a lysine 113(K113):glutamic acid 195 (E195) salt bridge between actin subunits, thus suggesting a molecular basis for actin catch-slip bonds. This structural mechanism is supported by the suppression of the catch bonds by the single-residue replacements K113 to serine (K113S) and E195 to serine (E195S) on yeast actin. These results demonstrate and provide a structural explanation for actin catch-slip bonds, which may provide a mechanoregulatory mechanism to control cell functions by regulating the depolymerization kinetics of force-bearing actin filaments throughout the cytoskeleton.
Details
- Title: Subtitle
- Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds
- Creators
- Cho-yin Lee - Wallace H. Coulter Department of Biomedical EngineeringJizhong Lou - Institute for Bioengineering and BiosciencesKuo-kuang Wen - Department of BiochemistryMelissa McKane - Department of BiochemistrySuzanne G Eskin - Wallace H. Coulter Department of Biomedical EngineeringShoichiro Ono - Department of PathologyShu Chien - Department of Bioengineering and Institute of Engineering in MedicinePeter A Rubenstein - Department of BiochemistryCheng Zhu - Wallace H. Coulter Department of Biomedical EngineeringLarry V McIntire - Wallace H. Coulter Department of Biomedical Engineering
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.110(13), pp.5022-5027
- DOI
- 10.1073/pnas.1218407110
- PMID
- 23460697
- PMCID
- PMC3612643
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Alternative title
- Actin catch-slip bonds
- Language
- English
- Date published
- 03/26/2013
- Academic Unit
- Stead Family Department of Pediatrics; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984024409302771
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