CSIR - Centre for Cellular & Molecular Biology
The Innovation Engine of India
Rajan Sankaranarayanan
Outstanding Scientist
Structural Biology
27192832
sankar@ccmb.res.in
Research Interests
Our laboratory is interested in exploring the mechanistic basis and functional relevance of unique proofreading mechanisms that are operational in the cell to maintain a high fidelity during translation of the genetic code. We are particularly interested in a D-aminoacyl-tRNA deacylase(DTD)-fold present in two functional contexts a) as an editing module of archaeal threonyl-tRNA synthetases and b) as a free standing domain responsible for \’Chiral proofreading i.e removal of D-amino acids mistakenly attached to tRNA. We are currently looking at the biological role of DTD using cell biological as well as in vivo approaches using model systems like drosophila and mouse. Structural biology work is underway on a couple of other proofreading systems for which the mechanism is not well understood.
Selected Publications
Kumar P, Roy A, Mukul SJ, Singh AK, Singh DK, Nalli A, Banerjee P, Babu KSD, Raman B, Kruparani SP, Siddiqi I, Sankaranarayanan R. (2024) A translation proofreader of archaeal origin imparts multialdehyde stress tolerance to land plants eLife https://doi.org/10.7554/eLife.92827.2
Kumar P, Babu KSD, Singh AK, Singh DK, Nalli A, Mukul SJ, Roy A, Mazeed M, Raman B, Kruparani SP, Siddiqi I, Sankaranarayanan R (2023) Distinct localization of chiral proofreaders resolves organellar translation conflict in plants. Proc Natl Acad Sci U S A. 2023 Jun 13;120(24):e2219292120. doi: 10.1073/pnas.2219292120. Epub 2023 Jun 5. PMID: 37276405; PMCID: PMC10268278.
Sivakumar K, Venkadasamy VL, Amudhan G, Ann KJ, Goud GK, Nayani K, Gogoi J, Kuncha SK, Mainkar PS, Kruparani SP, Sankaranarayanan R (2023) Design principles and functional basis of enantioselectivity of alanyl-tRNA synthetase and a chiral proofreader during protein biosynthesis. Nucleic Acids Res. 2023 Apr 24;51(7):3327-3340. doi: 10.1093/nar/gkad205. PMID: 36951106; PMCID: PMC10123102.
Mondal,S., Kinatukara,P., Singh, S., Shambhavi, S., Patil,G.S., Dubey,N., Singh,S.H., Pal,B., Shekar,P.C., Kamat,S.S., Sankaranarayanan, R. (2022) DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes. elife doi: 10.7554/eLife.77665.
Kumar, P., Bhatnagar, A. & Sankaranarayanan, R. (2022) Chiral Proofreading during protein biosynthesis and its evolutionary implications. FEBS Lett DOI: 10.1002/1873-3468.14419
Gogoi, J., Bhatnagar, A., Ann, K.J., Pottabathini, S., Singh, R., Mazeed, M., Kuncha, S.K., Kruparani, S.P., Sankaranarayanan, R. (2022) Switching a conflicted bacterial DTD-tRNA code is essential for the emergence of mitochondria. Sci. Adv. 8, eabj7307, 1-9. doi: 10.1126/sciadv.abj7307.
Education & Experience
P.G:
Physics ; Madurai Kamaraj ; 1990
Ph.D:
Biophysics ; Indian Institute of Science ; 1996
Post.Doc:
Structural Biology ; IGBMC, France ; 1996-2002
Team Members
Rajan Sankaranarayanan
Outstanding Scientist
P Shobha Krupa Rani
Scientist-F
Biswajit Pal
Scientist-F
P Sambhavi
Sr. Technical Officer (2)
Jotin Gogoi
Senior Research Fellow
Koushick S
Senior Research Fellow
Sakshi Shambhavi
Senior Research Fellow
Mukul J S
Junior Research Fellow
Santhosh K
Junior Research Fellow
Suhail Madhar Hanif S
Junior Research Fellow
Nisha Gupta
Junior Research Fellow
Priyam Chopra
Junior Research Fellow
Tamajit Biswas
Junior Research Fellow
Yogita Sharma
Junior Research Fellow
Subashree V
Project Associate
Azeen Zehra
Project Associate
Keerthana
Project Associate
Shankhadeep Baksi
Project Associate
Daityari Nayak
Project Associate
Anurag Bahadur
Project Associate
Publications
Title
Journal
Year
Distinct localization of chiral proofreaders resolves organellar translation conflict in plants.
Proc Natl Acad Sci U S A. doi: 10.1073/pnas.2219292120.
2023
Design principles and functional basis of enantioselectivity of alanyl-tRNA synthetase and a chiral proofreader during protein biosynthesis.
Nucleic Acids Res. doi: 10.1093/nar/gkad205.
2023
DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes.
elife doi: 10.7554/eLife.77665
2022
Chiral Proofreading during protein biosynthesis and its evolutionary implications
FEBS Lett DOI: 10.1002/1873-3468.14419
2022
Switching a conflicted bacterial DTD-tRNA code is essential for the emergence of mitochondria.
Sci. Adv. 8, eabj7307, 1-9. doi: 10.1126/sciadv.abj7307.
2022
A universal pocket in fatty acyl-AMP ligases ensures redirection of fatty acid pool away from coenzyme A-based activation
elife doi: 10.7554/eLife.70067
2021
Recruitment of Archaeal DTD is a Key Event Toward the Emergence of Land Plants.
Sci. Adv. 2021; 7 : eabe8890 DOI: 10.1126/sciadv.abe8890
2021
Chiral checkpoints during protein biosynthesis
J Biol Chem doi: 10.1074/jbc.REV119.008166
2019
A chiral selectivity relaxed paralog of DTD for proofreading tRNA mischarging in Animalia.
Nature Commun. 9:511 DOI: 10.1038/s41467-017-02204-w
2018
A discriminator code-based DTD surveillance ensures faithful glycine delivery for protein biosynthesis in bacteria.
elife doi: 10.7554/eLife.38232.
2018
Enzyme action at RNA-protein interface in DTD-like fold
Curr Opin Struct Biol. 53, 107-114.
2018
A Transition Metal-Binding, Trimeric ??-Crystallin from Methane-Producing Thermophilic Archaea, Methanosaeta thermophila.
Biochemistry 56, 1299-1310
2017
Role of D-aminoacyl-tRNA deacylase beyond chiral proofreading as a cellular defense against glycine mischarging by AlaRS. (Covered by a Spotlight article in TIBS, September 2017, vol. 42; p684)
Elife 6, e24001
2017
A mutation in an exoglucanase of Xanthomonas oryzae pv. oryzae, which confers an endo mode of activity, affects bacterial virulence, but not the induction of immune responses, in rice.
Mol Plant Pathol. doi: 10.1111/mpp.12620.
2017
Structural insights into the regulation of NADPH binding to reductase domains of nonribosomal peptide synthetases: A concerted loop movement model.
J. Struct. Biol. 194, 368-374.
2016
Elongation factor Tu prevents misediting of Gly-tRNA(Gly) caused by the design behind the chiral proofreading site of D-aminoacyl-tRNA deacylase.
PLOS Biol. 14(5) e1002465, 1-22.
2016
Mutations in the predicted active site of Xanthomonas oryzae pv. oryzae XopQ differentially affect virulence, suppression of host innate immunity and induction of HR in a non-host plant.
Mol. Plant Microbe Interact. 28, 195-206.
2015
Specificity and catalysis hardwired at the RNA-protein interface in a translational proofreading enzyme.
Nature Commun. 6:7552 doi: 10.1038/ncomms8552.
2015
Unsaturated Lipid Assimilation by Mycobacteria Requires Auxiliary cis-trans Enoyl CoA Isomerase.
Chemistry & Biology 22, 1577-1587.
2015
Delineating the reaction mechanism of reductase domains of Nonribosomal Peptide Synthetases from mycobacteria.
J. Struct. Biol. 187, 207-214.
2014
Decoding the molecular design principles underlying Ca(2+) binding to ??-crystallin motifs.
J. Mol. Biol. 415, 75-91.
2012
Molecular basis of the functional divergence of fatty acyl-AMP ligase biosynthetic enzymes of Mycobacterium tuberculosis.
J. Mol. Biol. 416, 221-238.
2012
Nonprocessive [2+2]e-off-loading reductase domains from mycobacterial nonribosomal peptide synthetases.
Proc. Natl. Acad. Sci. (USA) 109, 5681-5686.
2012
Crystallization and preliminary crystallographic studies of CbsA, a secretory exoglucanase from Xanthomonas oryzae pv. oryzae.
Acta Cryst. F68, 1191-1194.
2012
Aggregation prone near-native intermediate formation during unfolding of a structurally similar nonlenticular ??-crystallin domain.
Biochemistry 51, 8502-8513.
2012
Cloning, expression, purification, crystallization and preliminary X-ray crystallographic analyses of threonyl-tRNA synthetase editing domain from Aeropyrum pernix.
Acta Cryst. F68, 1390-1393.
2012
Signals and Pathways Regulating Nucleolar Retention of Novel Putative Nucleolar GTPase NGP-1(GNL-2).
Biochemistry 50, 4521-4536.
2011
In vitro evolved and non-aggregating and thermostable lipase: Structural and thermodynamic investigation.
J. Mol. Biol. 413, 726-741.
2011
Evolutionary and functional insights into Leishmania META1: evidence for lateral gene transfer and a role for META1 in secretion.
BMC Evol. Biol. 11, 334.
2011
Cloning, overexpression, purification, crystallization and preliminary X-ray analysis of a female-specific lipocalin (FLP) expressed in the lacrimal glands of Syrian hamsters.
Acta Cryst F66, 509-512.
2010
Vertebrate homologue of Drosophila GAGA factor.
J. Mol. Biol. 400, 434-447.
2010
Mechanistic insights into cognate substrate discrimination during proofreading in translation. (#Covered by an accompanying Commentary article in the same PNAS issue titled \\\'Proofreading in translation: Dynamics of the double-sieve model\\\' p21949-50)
Proc. Natl. Acad. Sci. (USA)107, 22117-22121.
2010
Three-Dimensional domain swapping in Nitrollin, a single-domain ??-Crystallin from Nitrosospira multiformis, controls protein conformation and stability but not dimerization.
J. Mol. Biol. 385, 163-177.
2009
Mechanistic and functional insights into fatty acid activation in Mycobacterium tuberculosis.
Nature Chem. Biol. 5, 166-173.
2009
Crystal structure of a fungal protease inhibitor from Antheraea mylitta.
J. Struct. Biol., 166, 79-87.
2009
A cell wall degrading esterase of Xanthomonas oryzae requires a unique substrate recognition module for pathogenesis on rice.
Plant Cell, 21,1860-1873.
2009
Betagamma-Crystallin superfamily contains a universal motif for binding calcium.
Biochemistry, 48, 12180-12190.
2009
Structural basis for the remarkable stability of Bacillus subtilis lipase at low pH.
Biochim. Biophys. Acta 1784, 302-311.
2008
ATPase activity of RecD is essential for growth of the Antarctic Pseudomonas syringae Lz4W at low temperature.
FEBS J. 27, 1835-1851.
2008
Structural insights into biosynthesis of resorcinolic lipids by a type III polyketide synthase in Neurospora crassa.
J. Struct. Biol. 162, 411-421.
2008
Exploring the limits of sequence and structure in a variant betagamma-crystallin domain of the protein absent in melanoma-1 (AIM1).
J. Mol. Biol. 381, 509-518.
2008
Thermostable Bacillus subtilis lipases: in vitro evolution and structural insight.
J. Mol. Biol. 381, 324-340.
2008
Betagamma-crystallins: A universal calcium-binding superfamily.
Protein Science, 17, suppl 1, pg.173.
2008
Crystallization and preliminary crystallographic studies of LipA, a secretory lipase/esterase from Xanthomonas oryzae pv. oryzae.
Acta Cryst. F63, 708-710.
2007
Crystallization and preliminary X-ray crystallographic investigations on a ??-Crystallin domain of Absent In Melanoma 1 (AIM1), a protein from Homo sapiens.
Acta Cryst. F62, 282-284.
2006
Crystallization and preliminary X-ray crystallographic studies of the N-terminal domain of FadD28, a fatty acyl AMP ligase from Mycobacterium tuberculosis.
Acta Cryst. F62, 350-352.
2006
Crystallization and preliminary X-ray diffraction analysis of a protease inhibitor from the haemolymph of the Indian tsar silkwork Antheraea mylitta.
Acta Cryst. F62, 669-671.
2006
Posttransfer editing mechanism of a D-aminoacyl-tRNA deacylase-like domain in threonyl-tRNA synthetase from archaea.
EMBO J. 25, 4152-4162.
2006
A Novel Lysine-rich Domain and GTP Binding Motifs Regulate the Nucleolar Retention of Human Guanine Nucleotide Binding Protein, GNL3L.
J. Mol. Biol. 364, 637-654.
2006
Crystal structure of low molecular weight protein tyrosine phosphatase (MPtpA) from Mycobacterium tuberculosis at 1.9
J. Bacteriol. 187, 2175-2181.
2005
A D-amino acid editing module coupled to the translational apparatus in archaea.
Nature Struct. Mol. Biol. 12, 556-557.
2005
Major histocompatibility complex class I polymorphism in Asiatic lions.
Tissue Antigens 66, 9-18.
2005
Crystallization and preliminary X-ray crystallographic investigations on several thermostable forms of a Bacillus subtilis lipase.
Acta Cryst. D60, 160-162.
2004
Crystallization and preliminary X-ray crystallographic investigations of an unusual type III polyketide synthase PKS18 from Mycobacterium tuberculosis.
Acta Cryst. D60, 749-751.
2004
A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites.
Nature Struct. Mol. Biol. 11, 894-900.
2004
Structural basis for selection and enhanced thermostability of laboratory evolved Bacillus subtilis lipase. 2004
J. Mol. Biol. 341, 1271-1281.
2004
Cloning, expression, purification, crystallization and preliminary X-ray crystallographic investigations on a unique editing domain from Archaebacteria.
Acta Cryst. D60, 1662-1664.
2004
PhyA, a secreted protein of Xanthomonas oryzae pv. oryzae, is required for optimum virulence and growth on phytic acid as a sole phosphate source.
Molecular Plant-Microbe Interactions 16, 973-982.
2003
A metal ion mediated functional dichotomy encodes plasticity during translation quality control.
Nat Commun https://doi.org/10.1038/s41467-025-58787-2
2025
A translation proofreader of archaeal origin imparts multialdehyde stress tolerance to land plants
eLife https://doi.org/10.7554/eLife.92827.2
2024
When Paul Berg meets Donald Crothers: an achiral connection through protein biosynthesis
Nucleic acids research, https://doi.org/10.1093/nar/gkae117
2024
Diacylglycerol metabolism and homeostasis in fungal physiology.
FEMS yeast research vol. 24: foae036.
2024
Genomic innovation of ATD alleviates mistranslation associated with multicellularity in Animalia. (Covered by elife Science Digest- \'Proofreading to evolve\' June 18 2020)
eLife 2020;9:e58118
2020
Mechanism of chiral proofreading during translation of the genetic code (#Highlighted as Science Editor\'s Choice article: \'Chirality Check\' Science Vol. 343, p119; 10thJanuary, 2014)
eLife 2:e01519
2013
Mechanism of chiral proofreading during translation of the genetic code (#Highlighted as Science Editor\\\'s Choice article: \\\'Chirality Check\\\' Science Vol. 343, p119; 10thJanuary, 2014)
eLife 2:e01519
2013
Mechanism of chiral proofreading during translation of the genetic code (#Highlighted as Science Editor\\\'s Choice article: \\\'Chirality Check\\\' Science Vol. 343, p119; 10thJanuary, 2014)
eLife 2:e01519
2013
Genomic innovation of ATD alleviates mistranslation associated with multicellularity in Animalia. (Covered by elife Science Digest- \\\'Proofreading to evolve\\\' June 18 2020)
eLife 2020;9:e58118
2020
Genomic innovation of ATD alleviates mistranslation associated with multicellularity in Animalia. (Covered by elife Science Digest- \\\'Proofreading to evolve\\\' June 18 2020)
eLife 2020;9:e58118
2020
Diacylglycerol metabolism and homeostasis in fungal physiology.
FEMS yeast research vol. 24: foae036.
2024
Diacylglycerol metabolism and homeostasis in fungal physiology.
FEMS yeast research vol. 24: foae036.
2024
When Paul Berg meets Donald Crothers: an achiral connection through protein biosynthesis
Nucleic acids research, https://doi.org/10.1093/nar/gkae117
2024
When Paul Berg meets Donald Crothers: an achiral connection through protein biosynthesis
Nucleic acids research, https://doi.org/10.1093/nar/gkae117
2024
A translation proofreader of archaeal origin imparts multialdehyde stress tolerance to land plants
eLife https://doi.org/10.7554/eLife.92827.2
2024
A translation proofreader of archaeal origin imparts multialdehyde stress tolerance to land plants
eLife https://doi.org/10.7554/eLife.92827.2
2024
A metal ion mediated functional dichotomy encodes plasticity during translation quality control.
Nat Commun https://doi.org/10.1038/s41467-025-58787-2
2025
A metal ion mediated functional dichotomy encodes plasticity during translation quality control.
Nat Commun https://doi.org/10.1038/s41467-025-58787-2
2025