Abstract

Proteins from the Protein Production Core produced in bacteria for crystal structure analysis will routinely be Se-Met labeled to directly enable phasing. For those produced in other hosts or initially provided by collaborators, additional approaches to phasing, such as via multiple isomorphous replacement methods as described below, will be used. The major objectives are (1) to develop crystallization and additive screens formulated specifically for protein complexes to optimize the probability of obtaining diffracting crystals and (2) to solve structures of HIV accessory/regulatory proteins using high-throughput approaches for crystallization, data collection, and structure determination. The ultimate goal is to solve the structures of HIV accessory/regulatory proteins in complexes with cellular proteins and to accomplish this by using rational approaches, as described throughout this proposal.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM082251-02
Application #
7671243
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
2
Fiscal Year
2008
Total Cost
$285,296
Indirect Cost

  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