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Lakkaraju SK, Hwang W. Modulation of elasticity in functionally distinct domains of the tropomyosin coiled-coil. Cell Mol Bioeng. 2009;2(1):57-65doi: 10.1007/s12195-009-0050-1.
Lakkaraju, S. K., & Hwang, W. (2009). Modulation of elasticity in functionally distinct domains of the tropomyosin coiled-coil. Cellular and molecular bioengineering, 2(1), 57-65. https://doi.org/10.1007/s12195-009-0050-1
Lakkaraju, Sirish Kaushik, and Hwang, Wonmuk. "Modulation of elasticity in functionally distinct domains of the tropomyosin coiled-coil." Cellular and molecular bioengineering vol. 2,1 (2009): 57-65. doi: https://doi.org/10.1007/s12195-009-0050-1
Lakkaraju SK, Hwang W. Modulation of elasticity in functionally distinct domains of the tropomyosin coiled-coil. Cell Mol Bioeng. 2009 Mar 01;2(1):57-65. doi: 10.1007/s12195-009-0050-1. PMID: 19830262; PMCID: PMC2760843.
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Cell Mol Bioeng. 2009 Mar 01;2(1):57-65. doi: 10.1007/s12195-009-0050-1.

Modulation of elasticity in functionally distinct domains of the tropomyosin coiled-coil.

Cellular and molecular bioengineering

Sirish Kaushik Lakkaraju, Wonmuk Hwang

Affiliations

  1. Department of Biomedical Engineering, Texas A&M University, College Station TX 77843 Tel.: +1-979-458-0178, , [email protected].

PMID: 19830262 PMCID: PMC2760843 DOI: 10.1007/s12195-009-0050-1

Abstract

Alpha-helical coiled-coils are common protein structural motifs. Whereas vast information is available regarding their structure, folding, and stability, far less is known about their elastic properties, even though they play mechanical roles in many cases such as tropomyosin in muscle contraction or neck stalks of kinesin or myosin motor proteins. Using computer simulations, we characterized elastic properties of coiled-coils, either globally or locally. Global bending stiffness of standard leucine zipper coiled-coils was calculated using normal mode analysis. Mutations in hydrophobic residues involved in the knob-into-hole interface between the two alpha-helices affect elasticity significantly, whereas charged side chains forming inter-helical salt bridges do not. This suggests that coiled-coils with less regular heptad periodicity may have regional variations in flexibility. We show this by the flexibility map of tropomyosin, which was constructed by a local fluctuation analysis. Overall, flexibility varies by more than twofold and increases towards the C-terminal region of the molecule. Describing the coiled-coil as a twisted tape, it is generally more flexible in the splay bending than in the bending of the broad face. Actin binding sites in alpha zones show local rigidity minima. Broken core regions due to acidic residues at the hydrophobic face such as the Asp137 and the Glu218 are found to be the most labile with moduli for splay and broad face bending as 70 nm and 116 nm respectively. Such variation in flexibility could be relevant to the tropomyosin function, especially for moving across the non-uniform surface of F-actin to regulate myosin binding.

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