Histone proteins package eukaryotic DNA into chromatin. The dynamic DNA-protein complex called nucleosomes form the basic element of chromatin. All eukaryotic genomic processes, both natural and pathological, including transcription, replication, recombination, repair, chromosome segregation, carcinogenesis and viral infection can be fully understood only in the context of nucleosomes. The core of a nucleosome, called the nucleosome core particle (NCP) consists of fourteen turns of B-form DNA around an octamer of histone proteins, as can be seen in the image towards the left.
Nucleosome is known to be the binding platform for several protein factors. In order for a protein to gain access to chromosomal DNA/histone proteins, it needs to interact and/or compete with the histone proteins/DNA of the nucleosome. Studies involving nucleosomes are of greater significance as compared to isolated studies focusing on interaction of protein factors with individual histone(s) or DNA. So in addition to a couple of stand-alone chromatin structural biology projects, we are also looking at projects which combine the themes of chromatin biology and infectious diseases. In this regard, our group is interested in proteins from certain viruses for which nucleosome form a docking station. A combined biochemical, biophysical and crystallographic approach on complexes of host nucleosomes and interacting viral proteins is expected to reveal details of the interactions, thereby explaining several previously unknown mechanisms involved in the life cycle of the viruses. This understanding could probably be a step towards the identification of suitable drug candidates against those viruses that target viral replication.
Around the theme of chromatin structural biology, another of our interest is histone chaperones. Histone chaperones are a group of proteins that bind histones and regulate nucleosome assembly. Mode of action of several histone chaperones is not well-understood. Also, it is not completely clear regarding what decides the specificity of certain histone chaperones for H3-H4, H2A-H2B or histone variants. In order to better understand these molecular machines, we work on a few projects dealing with the structural characterization of some important, but poorly characterized histone chaperones.
Within the broad area of infectious diseases, our group’s focus is primarily on crystallographic projects dealing with viral proteins and bacterial caseinolytic protease machinery proteins. Over and above these, additional crystallographic projects are being taken up from time to time, on a collaborative basis.
Our in-house collaborators:
Dr. Balachandran Ravindran (immunology)
Dr. Narottam Acharya (yeast genome instability)
Dr. Rajeeb Swain (vascular biology)
Dr. Soma Chattopadhyay (virology)
Dr. Tushar Kant Beuria (bacterial cell division)
Dr. Santhibhusan Senapati (tumor microenvironment)
Prof. Kim Lewis of North Eastern University, Boston, USA (mode of action of antibacterials)
Prof. Joo-Won Suh, Director of CNPM, Myongji University, South Korea (anti-TB agents)
Dr. Claudia Jonak, Austrian Institute of Technology, Tulln, Austria (plant stress signal transduction)
As we have technical expertise in making nucleosome core particles and nucleosomal arrays, our group is open to collaborative projects dealing with nucleosome binding factors.
Dileep Vasudevan, Gayathri Gopalan, Ashish Kumar, Veder J Garcia, Sheng Luan, Kunchithapadam Swaminathan. 2015. Plant immunophilins: a review of their structure-function relationship. Biochim Biophys Acta. 1850 (10): 2145-2158.
Dileep Vasudevan, Srinivasa P S Rao, Christian G Noble. 2013. Structural basis of mycobacterial inhibition by Cyclomarin A. Journal of Biological Chemistry 288 (43): 30883-30891.
Dileep Vasudevan, Aigen Fu, Sheng Luan, Kunchithapadam Swaminathan. 2012. Crystal structure of Arabidopsis thaliana cyclophilin 38 reveals a previously uncharacterized immunophilin fold and a possible autoinhibitory mechanism. Plant Cell 24 (6): 2666-2674.
Eugene Y D Chua*, Dileep Vasudevan*, Gabriela E Davey, Bin Wu, Curt A Davey. 2012. The mechanics behind DNA sequence-dependent properties of the nucleosome. Nucleic Acids Research 40 (13): 6338-6352. [* Equal contributors]
Dileep Vasudevan, Eugene Y D Chua, Curt A Davey. 2010. Crystal structures of nucleosome core particles containing the ‘601’ strong positioning sequence. Journal of Molecular Biology 403 (1): 1-10.
Ong S Michelle*, Dileep Vasudevan*, Curt A Davey. 2010. Divalent metal- & High Mobility Group N protein- dependent nucleosome stability and conformation. Journal of Nucleic Acids 2010 (Article ID 143890). [* Equal contributors]
Bin Wu, Mohideen A Kareem, Dileep Vasudevan, Curt A Davey. 2010. Structural insight into the sequence-dependence of nucleosome positioning. Structure 18 (4): 528-536.
Ou Li, Dileep Vasudevan, Curt A Davey, Peter Droge. 2006. High-level expression of DNA architectural factor HMGA2 and its association with nucleosomes in human embryonic stem cells. Genesis 44 (11): 523-529.
Dileep V, Kumar HS, Kumar Y, Nishibuchi M, Karunasagar I, Karunasagar I. 2003. Application of polymerase chain reaction for detection of Vibrio parahaemolyticus associated with tropical seafood and coastal environment. Letters in Applied Microbiology 36 (6): 423-427.