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Control of Collagen Stability and Heterotrimer Specificity through Repulsive Electrostatic Interactions
Center for Advanced Biotechnology and Medicine, Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, 679 Hoes Lane W, Piscataway, NJ 08854, USA
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Received: 29 October 2013; in revised form: 27 November 2013 / Accepted: 28 November 2013 / Published: 6 December 2013
Abstract: Charge-pair interactions between acidic and basic residues on the surface of collagen can promote stability as well as control specificity of molecular recognition. Heterotrimeric collagen peptides have been engineered de novo using either rational or computational methods, which in both cases optimize networks of favorable charge-pair interactions in the target structure. Less understood is the role of electrostatic repulsion between groups of like charge in destabilizing structure or directing molecular recognition. To study this, we apply a “charge crowding” approach, where repulsive interactions between multiple aspartate side chains are found to destabilize the homotrimer states in triple helical peptide system and can be utilized to promote the formation of heterotrimers. Neutralizing surface charge by increasing salt concentration or decreasing pH can enhance homotrimer stability, confirming the role of charge crowding on the destabilization of homotrimers via electrostatic repulsion. Charge crowding may be used in conjunction with other approaches to create specific collagen heterotrimers.
Keywords: triple-helix; circular dichroism; NMR; de novo design; molecular recognition
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Parmar, A.S.; Joshi, M.; Nosker, P.L.; Hasan, N.F.; Nanda, V. Control of Collagen Stability and Heterotrimer Specificity through Repulsive Electrostatic Interactions. Biomolecules 2013, 3, 986-996.
Parmar AS, Joshi M, Nosker PL, Hasan NF, Nanda V. Control of Collagen Stability and Heterotrimer Specificity through Repulsive Electrostatic Interactions. Biomolecules. 2013; 3(4):986-996.
Parmar, Avanish S.; Joshi, Mihir; Nosker, Patrick L.; Hasan, Nida F.; Nanda, Vikas. 2013. "Control of Collagen Stability and Heterotrimer Specificity through Repulsive Electrostatic Interactions." Biomolecules 3, no. 4: 986-996.