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You searched for +publisher:"University of North Carolina" +contributor:("Zhang, Jun"). One record found.

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University of North Carolina

1. Zhang, Jun. Structure and dynamics of the MAGUK core of PSD-95.

Degree: Biochemistry and Biophysics, 2011, University of North Carolina

Protein allostery plays central roles in regulation of enzyme catalysis, signaling conduction and cellular metabolism. In this research, the interdomain allostery of postsynaptic density protein 95 (PSD-95), a key component of the postsynapse, was studied using NMR and other biophysical methods. Previous research has identified numerous PSD-95 interaction partners and revealed many PSD-95 mediated biological functions. Interestingly, interdomain allostery within PSD-95 has been found between PDZ3 and the following SH3/GK, and these allosteric events are regulated by phosphorylation. However, the structural mechanism of interdomain allostery and phosphorylation regulation is not addressed by in vivo studies on biological functions or in vitro studies on excised domains. In this dissertation, we studied the structural and dynamic effects of phosphorylation at the PDZ3/SH3 linker (Y397, S415 and S418). Upon phosphorylation, we found that the C-extension α-helix of PDZ3 is unfolded and undocked. We further examined the PDZ3-SH3 construct and showed that phosphorylation interrupts the domain interaction between PDZ3 and SH3. Using chemical shift perturbation and paramagnetic relaxation enhancement, we identified the PDZ3-SH3 interface. These experiments also suggested that CRIPT binding moves PDZ3 away from SH3. To understand interdomain allostery, we modeled the PDZ3-SH3-GK structure using SAXS. Consistent with PRE results, we found PDZ3 is mainly docked to the Hook domain region of the SH3 domain, and CRIPT binding reshuffles the domain packing between PDZ3 and SH3-GK. To obtain a high resolution structural model of PDZ3-SH3-GK, we carried out Rosetta simulations in the presence of PRE and chemical shift perturbation constraints. We found that the PDZ3 domain uses its peptide binding groove to interact with the PDZ3-SH3 linker. This interaction brings PDZ3 close to SH3, whereas it can be disrupted by CRIPT binding. This Rosetta model also reveals that the positively charged face of the Hook domain, which is the binding interface for calmodulin, is masked by the PDZ3 domain. Therefore the model provides a basis for understanding interdomain allostery between SH3 and PDZ3. In this research we also discussed the possible mechanism by which PDZ3 and GK allostery is transferred. Advisors/Committee Members: Zhang, Jun, Lee, Andrew, University of North Carolina at Chapel Hill.

Subjects/Keywords: School of Medicine; Department of Biochemistry and Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Zhang, J. (2011). Structure and dynamics of the MAGUK core of PSD-95. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:f039ae75-0716-4a0b-a379-1691bbc4b994

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Zhang, Jun. “Structure and dynamics of the MAGUK core of PSD-95.” 2011. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:f039ae75-0716-4a0b-a379-1691bbc4b994.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Zhang, Jun. “Structure and dynamics of the MAGUK core of PSD-95.” 2011. Web. 21 Jan 2021.

Vancouver:

Zhang J. Structure and dynamics of the MAGUK core of PSD-95. [Internet] [Thesis]. University of North Carolina; 2011. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:f039ae75-0716-4a0b-a379-1691bbc4b994.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhang J. Structure and dynamics of the MAGUK core of PSD-95. [Thesis]. University of North Carolina; 2011. Available from: https://cdr.lib.unc.edu/record/uuid:f039ae75-0716-4a0b-a379-1691bbc4b994

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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