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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM082251-08
Application #
8727031
Study Section
Special Emphasis Panel (ZRG1-AARR-K)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
8
Fiscal Year
2014
Total Cost
$188,115
Indirect Cost
$63,947
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Gupta, Rupal; Lu, Manman; Hou, Guangjin et al. (2016) Dynamic Nuclear Polarization Enhanced MAS NMR Spectroscopy for Structural Analysis of HIV-1 Protein Assemblies. J Phys Chem B 120:329-39
Van Oss, S Branden; Shirra, Margaret K; Bataille, Alain R et al. (2016) The Histone Modification Domain of Paf1 Complex Subunit Rtf1 Directly Stimulates H2B Ubiquitylation through an Interaction with Rad6. Mol Cell 64:815-825
Perilla, Juan R; Gronenborn, Angela M (2016) Molecular Architecture of the Retroviral Capsid. Trends Biochem Sci 41:410-20
Sharaf, Naima G; Ishima, Rieko; Gronenborn, Angela M (2016) Conformational Plasticity of the NNRTI-Binding Pocket in HIV-1 Reverse Transcriptase: A Fluorine Nuclear Magnetic Resonance Study. Biochemistry 55:3864-73
Byeon, In-Ja L; Byeon, Chang-Hyeock; Wu, Tiyun et al. (2016) Nuclear Magnetic Resonance Structure of the APOBEC3B Catalytic Domain: Structural Basis for Substrate Binding and DNA Deaminase Activity. Biochemistry 55:2944-59
Saito, Akatsuki; Ferhadian, Damien; Sowd, Gregory A et al. (2016) Roles of Capsid-Interacting Host Factors in Multimodal Inhibition of HIV-1 by PF74. J Virol 90:5808-23
Ning, Jiying; Erdemci-Tandogan, Gonca; Yufenyuy, Ernest L et al. (2016) In vitro protease cleavage and computer simulations reveal the HIV-1 capsid maturation pathway. Nat Commun 7:13689
Rasheedi, Sheeba; Shun, Ming-Chieh; Serrao, Erik et al. (2016) The Cleavage and Polyadenylation Specificity Factor 6 (CPSF6) Subunit of the Capsid-recruited Pre-messenger RNA Cleavage Factor I (CFIm) Complex Mediates HIV-1 Integration into Genes. J Biol Chem 291:11809-19
Ramalho, Ruben; Rankovic, Sanela; Zhou, Jing et al. (2016) Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. Retrovirology 13:17
Oum, Yoon Hyeun; Desai, Tanay M; Marin, Mariana et al. (2016) Click labeling of unnatural sugars metabolically incorporated into viral envelope glycoproteins enables visualization of single particle fusion. J Virol Methods 233:62-71

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