Transcription Regulation: Structure and Mechanism

The hallmark of any living organism is the ability to respond to external stimuli and internal cues. These responses involve modulations in the gene expression profile of the organism. In order to ensure optimal use of resources, gene expression in bacteria is tightly regulated at the level of transcription initiation. In most cases the regulation of transcription initiation occurs through the use of factors that can positively (activators) or negatively (repressors) affect transcription. These factors may be global or specific depending on the number of genes and range of cellular functions that they modulate. They bind to specific DNA sequences within the promoter region and can either inhibit or stimulate the RNA polymerase (RNAP) activity. In addition, many of these molecules bind to small metabolites and this binding event affects their interaction with DNA to ultimately modulate transcription of the corresponding genes. Overall, transcription factors interact with target sequences on DNA, with other trans factors and with different subunits of RNAP to achieve function.

The primary focus of my laboratory is to investigate the relevant molecular interactions (protein-DNA, protein-small metabolites, protein-protein) that are critical for regulating the activity of RNAP. At present, the molecules under scrutiny are :

1. FleQ - a global transcription regulator of flagellar and biofilms genes in Pseudomonas aeruginosa.

2. AraR - a transcription repressor from Bacillus subtilis that serves to differentially repress enzymes involved in arabinose metabolism as well as its own expression.

We use an integrated approach involving structural tools, biophysical techniques and biochemical methods to shed light on these interactions.

• Amit Kumar Yadav
  Young Investigator
  [email protected]
• Chanchal
  Senior research fellow
  [email protected]
• Priyajit Banerjee
  Senior Research Fellow
  [email protected]
• Swatee Upadhyay
  Junior Research Fellow
  [email protected]
• Pankaj Kumar Sahoo
  Junior research fellow
  [email protected]
• Hemant Goswami
  Project JRF

1. Naskar T, Faruq M, Banerjee P, Khan M, Midha R, Kumari R, Devasenapathi R, Prajapati B, Sengupta S,  Jain D, Mukerji M, Singh NC, Sinha S (2018) Ancestral Variations of the PCDHG Gene Cluster Predispose to Dyslexia in a Multiplex Family EBioMedicine (In press) 
2. Chanchal, Banerjee P. and Jain D (2017) ATP-Induced Structural Remodeling in the Antiactivator FleN Enables Formation of the Functional Dimeric Form. Structure 25:252
3. Harshita, Chanchal and Jain D (2016)  Cloning, expression, purification, crystallization and initial crystallographic analysis of FleN from Pseudomonas aeruginosa. Acta Cryst. F72, 135
4. Jain D, Naveen Narayanan, Deepak T Nair (2015)   Plasticity in repressor-DNA interactions neutralizes loss of symmetry in bipartite operators Journal of Biological Chemistry 10.1074/jbc.M115.689695
5. Jain D (2015)  Allosteric control of transcription in GntR family of transcription regulators: A structural overview. IUBMB Life 67:556.
6. Jain D, Nair DT. (2013) Spacing between core recognition motifs determines relative orientation of AraR monomers on bipartite operators. Nucleic Acid Research, 41:639.
7. Twist, KA., Husnain, SI, Franke JD, Jain D, Campbell EA, Nickels, B.E Thomas, MS, Darst SA, Westblade LF (2011) A novel method for the production of in vivo-assembled, recombinant Escherichia coli RNA polymerase lacking the C- terminal domain Protein Science. 20:986.
8. Jain D, Lamour V. (2010) Computational tools in protein crystallography. Methods in Molecular Biology 673:129.
9. Namadurai S, Jain D, Kulkarni DS, Tabib CR, Friedhoff P, Rao DN, Nair DT. (2010) The C-terminal domain of the MutL homolog from Neisseria gonorrhoeae forms an inverted homodimer. PlosOne 5(10):e13726.
10. Jain D, Kim, Y, Maxwell, K.L, Beasley S, Zhang R, Gussin GN, Edwards A, Darst SA. (2005) Crystal Structure of Bacteriophage lambda cII and its DNA complex. Molecular Cell 19:259.
11. Jain D, Nickels BE, Sun L, Hochschild A, Darst SA. (2004) Structure of a Ternary Transcription Activation Complex. Molecular Cell 13:45.
12. Nagpal S, Kaur KJ, Jain D, Salunke DM. (2002) Plasticity in structure and interactions is critical for the action of indolicidin, an antibacterial peptide of innate immune origin
13. Chakraborty S, Chakraborty N, Jain D, Salunke DM, Datta A. (2002) Active site geometry of oxalate decarboxylase from Collybia velutipes: Role of histidine coordinated copper in substrate recognition Protein Science 11:2138.
14. Jain D, Nair DT, Swaminathan GJ, Abraham EG, Nagaraju J, Salunke DM. (2001) Structure of the Induced Antibacterial Protein from Tasar Silkworm, Antheraea mylitta: Implications to molecular evolution. J Biol Chem 276:41377.
15. Jain, D, Kaur KJ, Salunke DM. (2001). Plasticity in Protein-Peptide Recognition: Crystal Structures of Two Different Peptides Bound to Concanavalin A Biophys. J 80:2912.
16. Jain D, Kaur KJ, Salunke DM. (2001) Enhanced Binding of a Rationally Designed Peptide Ligand of Concanavalin A Arises From Improved Geometrical Complementarity. Biochemistry 40:12059.
17. Goel M, Jain D, Kaur KJ, Kenoth R, Maiya BG, Swamy MJ, Salunke DM. (2001) Functional equality in the absence of structural similarity: An added dimension to molecular mimicry. J Biol Chem 276:39277.
18. Kaur K, Jain D, Goel M, Salunke DM. (2001) Immunological Implications of Structural Mimicry between a Dodecapeptide and a Carbohydrate moiety Vaccine. 19:3124.
19. Jain D, Kaur K, Goel M, Salunke DM. (2000) Structural Basis of Functional Mimicry between Carbohydrate and Peptide Ligands of ConA. Biochem. Biophys. Res. Commun. 272:843.
20. Jain D, Kaur K, Sundaravadivel B, Salunke DM. (2000) Structural and Functional Consequences of Peptide-Carbohydrate Mimicry: Crystal Structure of a Carbohydrate-Mimicking Peptide Bound to Concanavalin. J Biol Chem 275:16098.