Restricted Research - Award List, Note/Discussion Page
Fiscal Year: 2023
1852 The University of Texas at El Paso (143740)
Principal Investigator: Xiao,Chuan
Total Amount of Contract, Award, or Gift (Annual before 2011): $ 300,000
Exceeds $250,000 (Is it flagged?): Yes
Start and End Dates: 6/1/22 - 5/31/25
Restricted Research: NO
Academic Discipline: Chemistry
Department, Center, School, or Institute: Chemistry
Title of Contract, Award, or Gift: Decipher the Biochemistry Folding and Assembly Mysteries of the Most Common Protein Motif Used by Viruses
Name of Granting or Contracting Agency/Entity:
WELCH FOUNDATION
Program Title: #N/A
Note:
A virus can be regarded as a “non-living” chemical macromolecular assembly. Viruses become “alive” after they enter the host cell. The de novo synthesis of viral proteins and their assembly into virus particles involve specific molecular mechanism of protein folding and intermolecular interactions, all of which are multi-step but highly controlled chemical reactions. The majority of viruses have capsids. The capsids protect the viral genomes, facilitate host recognitions, and deliver viral DNA or RNA into the host cells. Many viral capsids are self-assembled from a limited set of similar protein building blocks. The special constraints on these protein building blocks have resulted in the evolution of special protein folds, found only in viruses. One such example is the “jelly-roll fold” (JRF) used by almost 40% of all virus species. However, no consensus homologous sequences have been found for JRF. The goal of this project is to decipher the hidden chemistry of how various sequences can all fold into JRF and then ssemble into viral particles. In this study, the viral proteins of a common cold virus called Coxsackievirus A21 (CVA21) will be produced by cellular expression systems to mimic the viral protein synthesis and assembly in vitro. The PI will apply a combination of structural and traditional biochemical tools as well as artificial intelligence to study the folding of JFR viral protein in order to understand the mechanism of their assembly process. The results of the project will deepen our understanding of their folding and assembly mechanism so that wide-spectrum antiviral drugs can be developed. Furthermore, the results will shed light on how to effectively control protein-protein interactions that will facilitate the rational design of virus-like nanoparticles to be used for delivery of medicine as well as mRNA vaccines.
Discussion:
Withdrawn by institution.