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Integrative Structural and Computational Biology

Vijay S. Reddy, Ph.D.

Associate Professor
Department of Integrative Structural and Computational Biology
California Campus
Laboratory Website
reddyv@scripps.edu
(858) 784-8191

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

Our research interests are to determine the three dimensional structures of proteins and molecular assemblies such as viruses and to identify the structural underpinnings and requirements for the self-assembly, stability and targeting specificities of viral capsids. We further use this information as a knowledge base to design novel protein shells that polyvalently display multiple copies of peptides/proteins of interest. We employ X-ray crystallography, cryo-EM, computational, bioinformatics and genetic methods to investigate these areas of research.

Viruses are highly evolved macromolecular assemblages that perform a variety of functions during their life cycle: self-assemble to form uniform capsids, selective packaging of the genome, binding and followed by delivery of the genetic material to the susceptible target cells. Simple viruses such as non-enveloped viruses form capsids that are homogeneous in their composition and quaternary architecture. Hence are amenable for structural and functional analyses. 

In collaboration with Professor Glen Nemerow's group at TSRI, we recently determined the crystal structure of Human adenovirus at 3.5Å resolution (Reddy et al, 2010), the biggest virus structure yet determined to date. Highlights of the structure include novel conformation of the Penton base structure, where the fiber shaft is seen inserted deep into the PB-pore. One of the cement proteins, VIII has been conclusively identified located on the capsid interior at two different locations. Identification of other cement proteins are underway.

We are also actively involved in maintaining and developing the popular virus structure database, VIPERdb (http://viperdb.scripps.edu) of spherical virus structures and their computational and bio-informatics analysis (Carrillo-Tripp et al, 2009).

Reddy VS, Natchiar SK, Stewart PL, Nemerow GR. Crystal structure of human adenovirus at 3.5 A resolution. Science 2010; 329(5995): 1071-1075. 
Carrillo-Tripp M, Shepherd CM, Borelli IA, Venkataraman S, Lander G, Natarajan P, Johnson JE, Brooks CL, 3rd, Reddy VS. VIPERdb2: an enhanced and web API enabled relational database for structural virology. Nucleic Acids Res 2009;37(Database issue):D436-442.

Education

Ph.D., Molecular Biophysics, Indian Institute of Science, 1991

Professional Experience

Dr. Reddy obtained post-doctoral training in the Laboratory of Jack Johnson at TSRI, one of world leaders in the structural virology. On going collaborations with Dr. Glen Nemerow on the structural studies of human adenovirus; with Drs. Jack Johnson and Charles Brooks III (University of Michigan) on the maintaing and developing VIPERdb, a virus structure database.

Selected References

1. Reddy VS, Natchiar SK, Stewart PL, Nemerow GR. Crystal structure of human adenovirus at 3.5 A resolution. Science 2010;329(5995):1071-1075.

2. Reddy VS, Natchiar SK, Gritton L, Mullen TM, Stewart PL, Nemerow GR. Crystallization and preliminary X-ray diffraction analysis of human adenovirus. Virology 2010;402(1):209-214.

3. Nguyen HD, Reddy VS, Brooks CL, 3rd. Invariant polymorphism in virus capsid assembly. J Am Chem Soc 2009;131(7):2606-2614.

4. Nemerow GR, Pache L, Reddy V, Stewart PL. Insights into adenovirus host cell interactions from structural studies. Virology 2009;384(2):380-388.

5. Kumar S, Ochoa W, Singh P, Hsu C, Schneemann A, Manchester M, Olson M, Reddy V. Tomato bushy stunt virus (TBSV), a versatile platform for polyvalent display of antigenic epitopes and vaccine design. Virology 2009;388(1):185-190.

6. Carrillo-Tripp M, Shepherd CM, Borelli IA, Venkataraman S, Lander G, Natarajan P, Johnson JE, Brooks CL, 3rd, Reddy VS. VIPERdb2: an enhanced and web API enabled relational database for structural virology. Nucleic Acids Res 2009;37(Database issue):D436-442.

7. Venkataraman S, Reddy SP, Loo J, Idamakanti N, Hallenbeck PL, Reddy VS. Structure of Seneca Valley Virus-001: an oncolytic picornavirus representing a new genus. Structure 2008;16(10):1555-1561.

8. Venkataraman S, Reddy SP, Loo J, Idamakanti N, Hallenbeck PL, Reddy VS. Crystallization and preliminary X-ray diffraction studies of Seneca Valley Virus-001, a new member of the Picornaviridae family. Acta Crystallogr Sect F Struct Biol Cryst Commun 2008;64(Pt 4):293-296.

9. Pache L, Venkataraman S, Reddy VS, Nemerow GR. Structural variations in species B adenovirus fibers impact CD46 association. J Virol 2008;82(16):7923-7931.

10. Pache L, Venkataraman S, Nemerow GR, Reddy VS. Conservation of fiber structure and CD46 usage by subgroup B2 adenoviruses. Virology 2008;375(2):573-579.

11. Carrillo-Tripp M, Brooks CL, 3rd, Reddy VS. A novel method to map and compare protein-protein interactions in spherical viral capsids. Proteins 2008;73(3):644-655.

12. Nguyen HD, Reddy VS, Brooks CL, 3rd. Deciphering the kinetic mechanism of spontaneous self-assembly of icosahedral capsids. Nano Lett 2007;7(2):338-344.

13. Manayani DJ, Thomas D, Dryden KA, Reddy V, Siladi ME, Marlett JM, Rainey GJ, Pique ME, Scobie HM, Yeager M, Young JA, Manchester M, Schneemann A. A viral nanoparticle with dual function as an anthrax antitoxin and vaccine. PLoS Pathog 2007;3(10):1422-1431.

14. Lad SP, Yang G, Scott DA, Wang G, Nair P, Mathison J, Reddy VS, Li E. Chlamydial CT441 Is a PDZ Domain-Containing Tail-Specific Protease That Interferes with the NF-{kappa}B Pathway of Immune Response. J Bacteriol 2007;189(18):6619-6625.

15. Kumar S, Ochoa W, Kobayashi S, Reddy VS. Presence of a surface-exposed loop facilitates trypsinization of particles of Sinsiro virus, a genogroup II.3 norovirus. J Virol 2007;81(3):1119-1128.

16. Taylor DJ, Speir JA, Reddy V, Cingolani G, Pringle FM, Ball LA, Johnson JE. Preliminary x-ray characterization of authentic providence virus and attempts to express its coat protein gene in recombinant baculovirus. Arch Virol 2006;151(1):155-165.

17. Shepherd CM, Borelli IA, Lander G, Natarajan P, Siddavanahalli V, Bajaj C, Johnson JE, Brooks CL, 3rd, Reddy VS. VIPERdb: a relational database for structural virology. Nucleic Acids Res 2006;34(Database issue):D386-389.

18. Hsu C, Singh P, Ochoa W, Manayani DJ, Manchester M, Schneemann A, Reddy VS. Characterization of polymorphism displayed by the coat protein mutants of tomato bushy stunt virus. Virology 2006;349(1):222-229.

19. Shepherd CM, Reddy VS. Extent of protein-protein interactions and quasi-equivalence in viral capsids. Proteins 2005;58(2):472-477.

20. Reddy VS, Johnson JE. Structure-derived insights into virus assembly. Adv Virus Res 2005;64:45-68.

21. Natarajan P, Lander GC, Shepherd CM, Reddy VS, Brooks CL, 3rd, Johnson JE. Exploring icosahedral virus structures with VIPER. Nat Rev Microbiol 2005;3(10):809-817.

22. Mitra AK, Ren G, Reddy VS, Cheng A, Froger A. The architecture of a water-selective pore in the lipid bilayer visualized by electron crystallography in vitreous ice. Novartis Found Symp 2002;245:33-46; discussion 46-50; 165-168.

23. Damodaran KV, Reddy VS, Johnson JE, Brooks CL, 3rd. A general method to quantify quasi-equivalence in icosahedral viruses. J Mol Biol 2002;324(4):723-737.

24. Ren G, Reddy VS, Cheng A, Melnyk P, Mitra AK. Visualization of a water-selective pore by electron crystallography in vitreous ice. Proc Natl Acad Sci U S A 2001;98(4):1398-1403.

25. Reddy VS, Natarajan P, Okerberg B, Li K, Damodaran KV, Morton RT, Brooks CL, 3rd, Johnson JE. Virus Particle Explorer (VIPER), a website for virus capsid structures and their computational analyses. J Virol 2001;75(24):11943-11947.

26. Ren G, Cheng A, Reddy V, Melnyk P, Mitra AK. Three-dimensional fold of the human AQP1 water channel determined at 4 A resolution by electron crystallography of two-dimensional crystals embedded in ice. J Mol Biol 2000;301(2):369-387.

27. Oliveira AC, Gomes AM, Almeida FC, Mohana-Borges R, Valente AP, Reddy VS, Johnson JE, Silva JL. Virus maturation targets the protein capsid to concerted disassembly and unfolding. J Biol Chem 2000;275(21):16037-16043.

28. Bothner B, Schneemann A, Marshall D, Reddy V, Johnson JE, Siuzdak G. Crystallographically identical virus capsids display different properties in solution. Nat Struct Biol 1999;6(2):114-116.

29. Tsuruta H, Reddy VS, Wikoff WR, Johnson JE. Imaging RNA and dynamic protein segments with low-resolution virus crystallography: experimental design, data processing and implications of electron density maps. J Mol Biol 1998;284(5):1439-1452.

30. Schneemann A, Reddy V, Johnson JE. The structure and function of nodavirus particles: a paradigm for understanding chemical biology. Adv Virus Res 1998;50:381-446.

31. Reddy VS, Giesing HA, Morton RT, Kumar A, Post CB, Brooks CL, 3rd, Johnson JE. Energetics of quasiequivalence: computational analysis of protein-protein interactions in icosahedral viruses. Biophys J 1998;74(1):546-558.

32. Johnson JE, Reddy VS. Biggest virus molecular structure yet! Nat Struct Biol 1998;5(10):849-854.

33. Kumar A, Reddy VS, Yusibov V, Chipman PR, Hata Y, Fita I, Fukuyama K, Rossmann MG, Loesch-Fries LS, Baker TS, Johnson JE. The structure of alfalfa mosaic virus capsid protein assembled as a T=1 icosahedral particle at 4.0-A resolution. J Virol 1997;71(10):7911-7916.

34. Munshi S, Liljas L, Cavarelli J, Bomu W, McKinney B, Reddy V, Johnson JE. The 2.8 A structure of a T = 4 animal virus and its implications for membrane translocation of RNA. J Mol Biol 1996;261(1):1-10.

35. Zlotnick A, Reddy VS, Dasgupta R, Schneemann A, Ray WJ, Jr., Rueckert RR, Johnson JE. Capsid assembly in a family of animal viruses primes an autoproteolytic maturation that depends on a single aspartic acid residue. J Biol Chem 1994;269(18):13680-13684.

36. Wery JP, Reddy VS, Hosur MV, Johnson JE. The refined three-dimensional structure of an insect virus at 2.8 A resolution. J Mol Biol 1994;235(2):565-586.

37. Johnson JE, Munshi S, Liljas L, Agrawal D, Olson NH, Reddy V, Fisher A, McKinney B, Schmidt T, Baker TS. Comparative studies of T = 3 and T = 4 icosahedral RNA insect viruses. Arch Virol Suppl 1994;9:497-512.

38. Cheng RH, Reddy VS, Olson NH, Fisher AJ, Baker TS, Johnson JE. Functional implications of quasi-equivalence in a T = 3 icosahedral animal virus established by cryo-electron microscopy and X-ray crystallography. Structure 1994;2(4):271-282.

39. Reddy VS, Rao VS. Modes of binding of alpha (1-2) linked manno-oligosaccharides to concanavalin A. Int J Biol Macromol 1992;14(4):185-192.

Links

http://www.scripps.edu/~reddyv