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CSIR - Centre for Cellular & Molecular Biology
Council of Scientific and Industrial Research
Ministry of Science & Technology, Govt. of India
Outstanding Scientist
Email: sankar@ccmb.res.in
Phone: +91-040-27192832
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
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.
Patil G. S. , Kinatukara P., Mondal S., Shambhavi S., Patel K.D., Pramanik S., Dubey N., Narasimhan S., Madduri M K, Pal B, Gokhale R S, & Sankaranarayanan R. (2021) 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.
Mazeed, M. , Singh, R., Kumar P., Roy, A., Raman, B., Kruparani , S.P., & Sankaranarayanan, R. (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
Kuncha, S. K., Venkadasamy, V. L., Amudhan, G., Dahate, P., Kola, S.R., Pottabathini, S., Kruparani , S.P., Shekar, P.C. , & Sankaranarayanan, R. (2020) Genomic innovation of ATD alleviates mistranslation associated with multicellularity in Animalia. eLife 2020;9:e58118. (Covered by elife Science Digest- ‘Proofreading to evolve’ June 18 2020 https://elifesciences.org/digests/58118/proofreading-to-evolve )
Education & Experience
| P.G: | Physics ; Madurai Kamaraj ; 1990 |
| Ph.D: | Biophysics ; Indian Institute of Science ; 1996 |
| Post.Doc: | Structural Biology ; IGBMC, France ; 1996-2002 |
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| Title | Journal | Year |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
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