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On the theories of biomolecular interactions and their applications in intrinsic protein disorder and bacterial spore germination

Liu, Jintao (2012) On the theories of biomolecular interactions and their applications in intrinsic protein disorder and bacterial spore germination. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Living organisms are complex systems, where complexity arises in part from the large number of interacting components. Here I address interactions in two topics: intrinsically disordered proteins (IDP) and bacterial spore germination. In the first part, I study the role of intrinsic protein disorder in protein function with a standard thermodynamic model. IDPs are proteins without stable structure in their native states. Their ubiquitous presence undercuts the traditional view that a protein’s structure determines its function. Here I propose a quantitative theory that makes predictions regarding the role of intrinsic disorder in protein structure and function. By relating disorder with the free energy of folding, I show that both catalytic and low-affinity binding proteins prefer ordered structures, whereas high-affinity binding proteins can tolerate disorder. Relevant to both transcription and signal transduction, the theory also explains how increasing disorder can tune the binding affinity to maximize the specificity of promiscuous interactions. These claims are supported by a genome-wide survey of disorder. Collectively, the study provides insights into how natural selection acts on folding stability to optimize protein function. In the second part, I study the mechanism of the initiation of bacterial spore germination and propose a quantitative model. Spores are formed by some species of gram positive bacteria (e.g., Bacillus and Clostridium) during starvation. They are metabolically dormant and can later germinate into vegetative cells when nutrients (called germinants) reappear. The lag time of germination after encountering germinants is highly heterogeneous for spores in the same population, and the mechanism is still unclear. Here I propose a quantitative model based on the assumption that the heterogeneity is due to the variability in levels of activated germinant receptors (GR) per spore. The model produces predictions that are consistent with experiments on germination with mixtures of nutrients that trigger different types of GRs, which also suggests that signals from different GRs are summed by a common integrator.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Liu, Jintaojil41@pitt.eduJIL41
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCamacho, Carlosccamacho@pitt.eduCCAMACHO
Committee CoChairSalman, Hannahsalman@pitt.eduHSALMAN
Committee MemberCoalson, Robrob@mercury.chem.pitt.eduROBC
Committee MemberFaeder, Jamesfaeder@pitt.eduFAEDER
Committee MemberShepard, Paulshepard@pitt.eduSHEPARD
Committee MemberSnoke, Davidsnoke@pitt.eduSNOKE
Date: 1 February 2012
Date Type: Publication
Defense Date: 18 October 2011
Approval Date: 1 February 2012
Submission Date: 6 December 2011
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 105
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Physics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: binding, catalysis, intrinsic disorder, specificity, transcription, spore, germination, heterogeneity, signal processing, germinant receptor
Date Deposited: 01 Feb 2012 13:21
Last Modified: 15 Nov 2016 13:55

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  • On the theories of biomolecular interactions and their applications in intrinsic protein disorder and bacterial spore germination. (deposited 01 Feb 2012 13:21) [Currently Displayed]


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