This project seeks to discover and describe mechanisms of virus assembly, ultimately at near-atomic resolution and including an understanding of the dynamic and energetic aspects of virus capsid maturation. Objects to be studied include the head of bacteriophage HK97, with particular interest in capsid assembly, capsid maturation, and control and mechanism of covalent crosslinking;phage lambda tails, with particular interest in length determination and the role of assembly chaperones;phage lambda long tail fibers, with particular interest in the role and mode of interaction of an assembly chaperone; and the capsids of a group of phages with unusually large capsids, with particular interest in how large capsid sizes are determined accurately. This work will enhance our understanding of virus life cycles and of molecular machines. The group of viruses under study shares many of the features of its assembly and maturation with animal viruses, especially including Herpesvirus, so these studies have the potential to enhance our understanding of human pathogens.

Public Health Relevance

This project studies the structure of viruses and the way virus particles are assembled in the infected cell from their component proteins and DNA. This will advance understanding of virus life cycles and so potentially our ability to disrupt those life cycles. The specific viruses under study, bacteriophages, do not directly cause human disease, but they share many similarities with human viruses, particularly the Herpes viruses.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM047795-36
Application #
8310060
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Sakalian, Michael
Project Start
1977-12-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
36
Fiscal Year
2012
Total Cost
$529,020
Indirect Cost
$169,392
Name
University of Pittsburgh
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Cardone, Giovanni; Duda, Robert L; Cheng, Naiqian et al. (2014) Metastable intermediates as stepping stones on the maturation pathways of viral capsids. MBio 5:e02067
Xu, Jun; Hendrix, Roger W; Duda, Robert L (2014) Chaperone-protein interactions that mediate assembly of the bacteriophage lambda tail to the correct length. J Mol Biol 426:1004-18
Oh, Bonnie; Moyer, Crystal L; Hendrix, Roger W et al. (2014) The delta domain of the HK97 major capsid protein is essential for assembly. Virology 456-457:171-8
Pope, Welkin H; Jacobs-Sera, Deborah; Russell, Daniel A et al. (2014) Genomics and proteomics of mycobacteriophage patience, an accidental tourist in the Mycobacterium neighborhood. MBio 5:e02145
Tso, Dan-ju; Hendrix, Roger W; Duda, Robert L (2014) Transient contacts on the exterior of the HK97 procapsid that are essential for capsid assembly. J Mol Biol 426:2112-29
Duda, Robert L; Oh, Bonnie; Hendrix, Roger W (2013) Functional domains of the HK97 capsid maturation protease and the mechanisms of protein encapsidation. J Mol Biol 425:2765-81
Smith, Margaret C M; Hendrix, Roger W; Dedrick, Rebekah et al. (2013) Evolutionary relationships among actinophages and a putative adaptation for growth in Streptomyces spp. J Bacteriol 195:4924-35
Pietila, Maija K; Laurinmaki, Pasi; Russell, Daniel A et al. (2013) Structure of the archaeal head-tailed virus HSTV-1 completes the HK97 fold story. Proc Natl Acad Sci U S A 110:10604-9
Xu, Jun; Hendrix, Roger W; Duda, Robert L (2013) A balanced ratio of proteins from gene G and frameshift-extended gene GT is required for phage lambda tail assembly. J Mol Biol 425:3476-87
Hendrix, Roger W; Johnson, John E (2012) Bacteriophage HK97 capsid assembly and maturation. Adv Exp Med Biol 726:351-63

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