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 #
5P50GM082251-07
Application #
8546396
Study Section
Special Emphasis Panel (ZRG1-AARR-K)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
7
Fiscal Year
2013
Total Cost
$181,533
Indirect Cost
$61,709

  Institution

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

  Publications

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
Ning, Jiying; Zhong, Zhou; Fischer, Douglas K et al. (2018) Truncated CPSF6 Forms Higher-Order Complexes That Bind and Disrupt HIV-1 Capsid. J Virol 92:
Himes, Benjamin A; Zhang, Peijun (2018) emClarity: software for high-resolution cryo-electron tomography and subtomogram averaging. Nat Methods 15:955-961
Balasubramaniam, Muthukumar; Zhou, Jing; Addai, Amma et al. (2018) PF74 Inhibits HIV-1 Integration by Altering The Composition of the Preintegration Complex. J Virol :
Lu, Manman; Sarkar, Sucharita; Wang, Mingzhang et al. (2018) 19F Magic Angle Spinning NMR Spectroscopy and Density Functional Theory Calculations of Fluorosubstituted Tryptophans: Integrating Experiment and Theory for Accurate Determination of Chemical Shift Tensors. J Phys Chem B 122:6148-6155

Showing the most recent 10 out of 144 publications