Design and Structural Characterization of Self-Assembling Triple Helical Heterotrimers

dc.contributor.advisorHartgerink, Jeffrey D.en_US
dc.contributor.committeeMemberWolynes, Peter G.en_US
dc.contributor.committeeMemberTao, Yizhi Janeen_US
dc.creatorFallas Valverde, Jorgeen_US
dc.date.accessioned2013-06-05T15:59:25Zen_US
dc.date.accessioned2013-06-05T16:00:02Zen_US
dc.date.available2013-06-05T15:59:25Zen_US
dc.date.available2013-06-05T16:00:02Zen_US
dc.date.created2012-12en_US
dc.date.issued2013-06-05en_US
dc.date.submittedDecember 2012en_US
dc.date.updated2013-06-05T16:00:02Zen_US
dc.description.abstractDesign of self-assembling ABC-type collagen triple helical heterotrimers is challenging due to the number of competing species that can be formed in ternary mixture of peptides with a high propensity to fold into triple helices and the fact that well understood rules for pair-wise amino acid stabilization of the canonical collagen triple helix have remained elusive. Given the required one amino acid stagger between adjacent peptide strands in this fold, a ternary mixture of peptides can form as many as 27 triple helices with unique composition or register. Previously we have demonstrated that electrostatic interactions can be used to bias the helix population towards a desired target but the presence of competing states in mixtures has remained an outstanding problem. In this work we use high-resolution structural biology techniques to do a detailed study of stabilizing pair-wise interactions between positively and negatively charged amino acids in triple helices. Two types of contacts with distinct sequence requirements depending on the relative stagger of the interacting chains are observed: axial and lateral. Such register-specific interactions are crucial for the understanding of the registration process of collagens and the overall stability of proteins in this family. Using this knowledge we developed distinct design strategies to improve the specificity of our designed systems towards the desired ABC heterotrimeric target state. We validate our strategies through the synthesis and characterization of the designed sequences and show that they self-assemble into a highly stable ABC triple helices with control over composition in the case of the rational approach and with control over both composition and register in the case of the computational approach.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationFallas Valverde, Jorge. "Design and Structural Characterization of Self-Assembling Triple Helical Heterotrimers." (2013) Diss., Rice University. <a href="https://hdl.handle.net/1911/71303">https://hdl.handle.net/1911/71303</a>.en_US
dc.identifier.slug123456789/ETD-2012-12-239en_US
dc.identifier.urihttps://hdl.handle.net/1911/71303en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectPeptide chemistryen_US
dc.subjectSupramolecular chemistryen_US
dc.subjectSelf-assemblyen_US
dc.subjectCollagenen_US
dc.subjectNMRen_US
dc.subjectProtein crystallographyen_US
dc.titleDesign and Structural Characterization of Self-Assembling Triple Helical Heterotrimersen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentChemistryen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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