Abstract

Project 3. A hallmark of HIVs success is rooted in extreme sequence variability, and recent deep sequencing efforts are increasing the amount of available data dramatically^^?. 28) Most previous sequence analysis focused on gpi20 sequences due to its direct interaction with the host immune system. While HFV sequences diverge, they do so under evolutionary pressures, and sequences are, therefore, a formidable source of information to identify the role that individual amino acids play in functional properties. HIV sequence variability impacts not only envelope but all HIV proteins, and we propose to focus on CA. The major evolutionary constraints on CA are associated with its structural integrity, its dynamic properties during assembly and disassembly, and its interaction sites with host proteins. We plan to exploit HIV and SIV sequence data to carry out an analysis of CA protein sequence variability and explore its impact on capsid structure, dynamics, and function.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
2P50GM082251-06
Application #
8528172
Study Section
Special Emphasis Panel (ZRG1-AARR-K (50))
Project Start
Project End
Budget Start
2012-09-30
Budget End
2013-07-31
Support Year
6
Fiscal Year
2012
Total Cost
$456,958
Indirect Cost
$110,718

  Institution

Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Quinn, Caitlin M; Wang, Mingzhang; Polenova, Tatyana (2018) NMR of Macromolecular Assemblies and Machines at 1 GHz and Beyond: New Transformative Opportunities for Molecular Structural Biology. Methods Mol Biol 1688:1-35
Hadden, Jodi A; Perilla, Juan R (2018) All-atom virus simulations. Curr Opin Virol 31:82-91
Yan, Junpeng; Shun, Ming-Chieh; Hao, Caili et al. (2018) HIV-1 Vpr Reprograms CLR4DCAF1 E3 Ubiquitin Ligase to Antagonize Exonuclease 1-Mediated Restriction of HIV-1 Infection. MBio 9:
Dick, Robert A; Zadrozny, Kaneil K; Xu, Chaoyi et al. (2018) Inositol phosphates are assembly co-factors for HIV-1. Nature 560:509-512
Martin, Jessica L; Mendonça, Luiza M; Marusinec, Rachel et al. (2018) Critical Role of the Human T-Cell Leukemia Virus Type 1 Capsid N-Terminal Domain for Gag-Gag Interactions and Virus Particle Assembly. J Virol 92:
Wang, Mingzhang; Lu, Manman; Fritz, Matthew P et al. (2018) Fast Magic-Angle Spinning 19 F?NMR Spectroscopy of HIV-1 Capsid Protein Assemblies. Angew Chem Int Ed Engl 57:16375-16379
Paramasivam, Sivakumar; Gronenborn, Angela M; Polenova, Tatyana (2018) Backbone amide 15N chemical shift tensors report on hydrogen bonding interactions in proteins: A magic angle spinning NMR study. Solid State Nucl Magn Reson 92:1-6
Fritz, Matthew; Quinn, Caitlin M; Wang, Mingzhang et al. (2018) Determination of accurate backbone chemical shift tensors in microcrystalline proteins by integrating MAS NMR and QM/MM. Phys Chem Chem Phys 20:9543-9553
Quinn, Caitlin M; Wang, Mingzhang; Fritz, Matthew P et al. (2018) Dynamic regulation of HIV-1 capsid interaction with the restriction factor TRIM5? identified by magic-angle spinning NMR and molecular dynamics simulations. Proc Natl Acad Sci U S A 115:11519-11524
Varlakhanova, Natalia V; Alvarez, Frances J D; Brady, Tyler M et al. (2018) Structures of the fungal dynamin-related protein Vps1 reveal a unique, open helical architecture. J Cell Biol 217:3608-3624

Showing the most recent 10 out of 144 publications