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.
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.
Structural Biology of Clp Machinery Proteins
The caseinolytic protease (Clp) machinery is present in bacteria, plants and other eukaryotes. These proteases usually associate with Clp chaperone proteins which help in ATP-dependent unfolding of substrates which need to be taken in for proteolysis by the proteases. ClpD is a Clp-associated chaperone unique to plants. Plant ClpC and ClpD proteins both get localized into chloroplast stroma. However, our recent work has revealed that the structure of ClpD is quite different from ClpC in its N-terminus. Our interest on plant Clp machinery proteins is to understand their distinct roles in protein homeostasis and stress response. In addition, we also work on mycobacterial Clp chaperones due to their importance as a target in anti-mycobacterial research.
Infectious Disease Structural Biology
A couple of our chromatin structural biology and Clp machinery projects have infectious disease flavour. In addition, we also work on proteins involved in bacterial cell division, as well as proteins from infectious fungal and viral pathogens. More recently, we have started working on candidate proteins from the dreaded White Spot Syndrome Virus (WSSV) that infects cultured shrimps.
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. Soumen Chakraborty (leukemia)
Dr. Santhibhusan Senapati (tumor microenvironment)
Dr. Narottam Acharya (yeast genome instability)
Dr. Soma Chattopadhyay (virology)
Dr. Tushar Kant Beuria (bacterial cell division)
Other major collaborators:
Prof. Kim Lewis, North Eastern University, Boston, USA (antibacterials)
Prof. Joo-Won Suh, Myongji University, S. Korea (anti-TB agents)
Prof. Sheng Luan, University of California at Berkeley, USA (plant FKBPs)
Prof. Klaas van Wijk, Cornell University, USA (plant protein homeostasis)
Prof. Claudia Jonak, Austrian Inst. of Technology, Austria (plant stress factors)
Prof. Anil Grover, University of Delhi-South Campus, India (plant stress tolerance)
Prof. Jagnehswar Dandapat, Utkal University, India (immunology)
Prof. Rabindra Behera, NIT-Rourkela, India (ferritin nanocages)
Prof. Anirban Bhunia, Bose Institute, Kolkata (protein NMR)
Dr. Devinder Sehgal, National Institute of Immunology, New Delhi (bacterial virulence)
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.
Chinmayee Mohapatra, Manas Kumar Jagdev, Dileep Vasudevan. 2017. Arabidopsis ClpD N-terminal domain is highly divergent from ClpC1. XXIV IUCr Congress Abstract. Acta Crystallographica A A73 A2, C246.
Dileep Vasudevan, Manas Kumar Jagdev, Chinmayee Mohapatra. 2017. Structural basis of mycobacterial inhibition by natural products targeting ClpC1. XXIV IUCr Congress Abstract. Acta Crystallographica A A73 A2, C228.
Biswamaitree Subhadarshanee*, Abhinav Mohanty*, Manas Kumar Jagdev, Dileep Vasudevan, Rabindra Kumar Behera. 2017. Surface charge dependent separation of modified and hybrid ferritin in native PAGE: impact of lysine 104. Biochimica et Biophysica Acta – Proteins and Proteomics1865 (10): 1267-1273.
Chinmayee Mohapatra*, Manas Kumar Jagdev*, Dileep Vasudevan. 2017. Crystal structures reveal N-terminal Domain of Arabidopsis thaliana ClpD to be highly divergent from that of ClpC1. Scientific Reports 7: 44366
Dileep Vasudevan*, Gayathri Gopalan*, Ashish Kumar, Veder J Garcia, Sheng Luan, Kunchithapadam Swaminathan. 2015. Plant immunophilins: a review of their structure-function relationship. Biochimica et Biophysica Acta– General Subjects1850 (10): 2145-2158.
Dileep Vasudevan, Srinivasa P S Rao, Christian G Noble. 2013. Structural basis of mycobacterial inhibition by Cyclomarin A. Journal of Biological Chemistry288 (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.
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).
Bin Wu*, Mohideen A Kareem*, Dileep Vasudevan, Curt A Davey. 2010. Structural insight into the sequence-dependence of nucleosome positioning.Structure18 (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. Genesis44 (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 Microbiology36 (6): 423-427.
[* Equal contributors]
Our Group Photo:
1. Mr. Ruchir Chandrakant Bobde(JRF) – PhD scholar
BCIL trainee in Imgenex India Pvt. Ltd., Bhubaneswar, 2007-2008.
JRF/SRF in CIFA, Bhubaneswar, 2008-2014.
ILS Institutional postdoc from April 2014 to July 2014.
Postdoc in ILS with DBT-RA fellowship from July 2014 to June 2016.
Postdoc in ILS with SERB N-PDF from July 2016 to June 2018.
While with us, she worked on Bacterial & Plant Protease Machinery Proteins.
Currently working as a Guest Faculty at Ravenshaw University.
Title of the project
Structural characterization of White Spot Syndrome Viral enzymes involved in viral nucleotide synthesis
3 years; from January 2018
Structural basis of dengue virus capsid protein interaction with the human death domain-associated protein DAXX
3 years; from October 2015
Host nucleosomes forming a docking station for Dengue virus capsid protein C – a structural analysis
3 years; from October 2015
Structural characterization of Influenza A virus matrix protein M1 interaction with host nucleosomes
3 years; from November 2014 (completed)
dileepvasudevan [at] gmail [dot] com, dileep [at] ils [dot] res [dot] in
Nalco Square, Bhubaneswar-751023, India
Dileep’s write-up on the building of his research group at ILS got featured in StoriesInScience, an online forum and repository that posts inspiring stories in science from around the world. You can read the story here: