Musti V. Krishnasastry, Ph. D.        

Research interests:

Our laboratory is interested in studying the protein-membrane, protein-protein interactions and derailment of signal transduction mechanisms orchestrated by membrane interacting proteins. For example we study the mode of binding and modulation of signal pathways by pore forming toxin, α-hemolysin from Staphylococcus aureus, Mycobacterium tuberculosis and other   pathogenic bacteria in detail.  We focus on the interaction of these proteins with cell membranes, the components involved in their interaction with an ultimate goal to elucidate the consequences and membrane protein assembly.  We also study some plant proteins, which parallel these proteins from pathogenic bacteria in some aspects.  The ultimate goals of the laboratory are to design protein with specific functions to target certain signal transduction pathways that originate at cell surface receptors.  Currently, the EGFr model system is being studied.  We proposed a protein-protein interaction based mechanism for the assembly of 14- strand β-barrel of staphylococcal α-hemolysin.

Our recent publications:

1. Vandana, S., Manoj, R. and Krishnasastry, M.V., (1997), The Role of the amino terminus in the kinetics and assembly of α-hemolysin of Staphylococcus aureus. J. Biol. Chem., 272, 24858-24863.

2. Sangha, N., Surinder, K., Vandana, S. and Krishnasastry, M.V., (1999), Importance of carboxy terminus in the folding and function of α-hemolysin of Staphylococcus aureus.  J. Biol. Chem., 274, 9193-9199.

3. Shen, Y., Krishinasastry, M. V., Hiramoto, M., Kikuchi, H., Kawarabayashi, Y., and Matsui, I. (2001)  Invariant Asp1122 and Asp1124 are essential residues for polymerization catalysis of family D DNA polymerase from Pyrococcus horikoshii  J. Biol. Chem. 276, 27376-27383.

4. Zheng R, Matsui E, Shen Y, Musti KV, Feng Y, Darnis S, KawarabayasiY,   Kikuchi H, Harata K, Matsui I. (2001) The novel function of a shortregion K253xRxxxD259 conserved in the exonuclease domain of hyperthermostable DNA polymerase I from Pyrococcus horikoshii. Extremophiles  5, 111-117.

5. Bachhawat, K., Thomas, C. J., Amutha, B., Krishnasastry, M. V., Khan, M. I., Surolia, A. (2001) On the stringent requirement of mannosyl substitution in mannooligo-saccharides for the recognition by garlic (Allium sativum) lectin: A surface plasmon resonance study.  J. Biol. Chem. 276, 5541-5546.

6. Matsui, E., Krishnasastry, M.V., Abe, J., Matsui, I. K. and Harata, K. (2002)  Molecular structure and novel DNA binding sites located in loops of flap endonuclease-1. J. Biol. Chem. 277, 37840-37847.

7. Sharma, V., Sangha, N., Kaur, S. and Krishnasastry, M. V. (2003) Modulation of EGF receptor autophosphorylation by α-hemolysin of Staphylococcus aureus via protein tyrosine phosphatase, FEBS lett. 535, 71-76.

8. Kapoor. M., Reddy, C.C., Krishnasastry, M.V., Surolia, N., Surolia, A. (2004) Slow-tight binding inhibition of enoyl-acyl carrier protein reductase from Plasmodium falciparum by triclosan. Biochem. J. 381, 719-724.

9. Pany, S., Vijayvargia, R., and Krishnasastry, M. V. (2004) Caveolin-1 binding motif of α-hemolysin: its role in stability and pore formation. Biochem. Biophys. Res. Commun. 322, 29-36.

10. Sahasrabuddhe, A., Gaikwad, S. M., Krishnasastry, M. V. and Khan, M. I. (2004) Studies on recombinant single chain jacalin lectin reveal loss of affinity for saccharides despite normal folding like native Jacalin. Protein Science. 13, 3264-3273.

11. Vijayvargia, R., Kaur, S., Sangha, N., Sahasrabuddhe, A., Surolia, I., Shouche, Y. and Krishnasastry, M. V. (2004) Assembly of α-hemolysin on A431 cells leads to clustering of Caveolin-1. Biochem. Biophys. Res. Commun. 324, 1124-1129.

12. Vijayvargia, R. Suresh, G. C. and Krishnasastry, M. V. (2004) Functional form of Caveolin-1 is necessary for the assembly of α-hemolysin. Biochem. Biophys. Res. Commun. 324, 1130-1137.

13. Vijayvargia, R., Kaur, S. and Krishnasastry, M. V. (2004) Staphylococcal α-HL induced dephosphorylation of EGF receptor of A431 cells is carried out by receptor like protein tyrosine phosphatase σ. Biochem. Biophys. Res. Commun. 325, 344-352.

Current group:

Mr. Anil Lotke, Technician 

Mr. Anagh Sahasrabuddhe, Senior Research Fellow

Mr. Satyabrata Pany, Senior Research Fellow

Miss. Swaroop Soumya, Junior Research Fellow

Miss. Amita Sneh, Junior Research Fellow

Mr. Nessar Ahmed, Junior Research Fellow

Mr. Aejazur Rehman, Junior Research Fellow

Contact Info :

National Center for Cell Science

NCCS Complex, Ganeshkind

Pune 411 007, Maharashtra, India

Ph.: 91-20-2569 0922 (extn. 320)

Fax: 91-20-2569 2259

Email: mvks@nccs.res.in 

Other publications:

1. Krishnasastry, M.V., Narasimhulu, P.L. and Sen, K.D.(1984) J. Chem. Phys. 80, 584-585 (Master of Science dissertation) 

2. Swamy, M.J., Krishnasastry, M.V. and Surolia, A. (1985) J. Biosci., 9, 203-212.

3. Krishnasastry, M. V., Banerjee, P., Patanjali, S. R., Swamy, M.J., Swarnalata, G.V. and Surolia, A. (1986) Analysis of saccharide binding to Artocarpus integrifolia lectin reveals specific recognition of T-antigen (β-D-Gal(1→3)D-GalNAc). J. Biol. Chem. 261, 11726-11733

4. Krishnasastry, M. V. and Surolia, A. (1986) Intrinsic fluorescence studies on saccharide binding to Artocarpus integrifolia lectin. Biosci. Reports, 6,853-860.

5. Khan, M. I., Krishnasastry, M.V. and Surolia, A.(1986) Thermodynamic and kinetic analysis of carbohydrate binding to the basic lectin from winged bean (Psophocarpus tetragonolobus). J. Biol. Chem. 261, 3013-3019.

6. Swamy, M.J., Krishnasastry, M.V., Khan, M.I. and Surolia, A. (1986) Thermodynamic and kinetic studies on saccharide binding to soya-bean agglutinin. Biochem. J. 234, 515-522

7. Krishnasastry, M. V., Swamy, M.J. and Surolia, A.(1989) Analysis of dynamics and mechanism of ligand binding to Artocarpus integrifolia agglutinin. A ¹³C and ¹⁹F NMR study. J. Biol. Chem. 263, 14826-14833

8. Khan. M.I., Swamy, M.J., Krishnasastry, M.V., Sajjan, S.U., Patanjali, S.R., Swarnalata, G.V., Banerjee, P. and Surolia, A. (1988) Glycoconjugates J., 5, 75

9. Mahanta, S.K., Krishnasastry, M.V. and Surolia, A. (1990) Topography of the combining region of a Thomsen-Friedenreich antigen-specific lectin jacalin (Artocarpus integrifolia agglutinin). A thermodynamic and circular-dichroism spectroscopic study.  Biochem. J. 265, 851-840.

10. Krishnasastry, M.V., Robertson, D.E., Mohyniham, J.A. and Roberts, M. F. (1992) Enzymatic degradation of cyclic 2,3-diphosphoglycerate to 2,3-diphosphoglycerate in Methanobacterium thermoautotrophicum. Biochemistry, 31, 2926-2935

11. Krishnasastry, M.V., Walker, B.J.,Zorn,L., Kasianowicz, J. and Bayley, H. (1992) in "Synthetic microstructures in Biological Research" (Eds. Schnur. J.M. amd Peckerar, M.) Plenum Press, New York, pp 41-51.

12. Walker, B.J., Krishnasastry, M.V., Zorn, L., Kasianowicz, J., and Bayley, H. (1992) Functional expression of the α-hemolysin of Staphylococcus aureus in intact Escherichia coli and in cell lysates. Deletion of five C-terminal amino acids selectively impairs hemolytic activity. J. Biol. Chem. 267, 10902-10909.

13. Walker, B.J. and Krishnasastry, M.V. Zorn, L., and Bayley, H. (1992) Assembly of the oligomeric membrane pore formed by staphylococcal α-hemolysin examined by truncation mutagenesis. J. Biol. Chem. 267, 21782-21786.

14. Walker, B.J., Krishnasastry, M.V., and Bayley, H.(1993)  Functional complementation of staphylococcal α-hemolysin fragments. Overlaps, nicks, and gaps in the glycine-rich loop. J. Biol. Chem. 268, 5285-5292.

15. Walker, B.J., Kasianowicz, J. Krishnasastry, M., and Bayley, H.(1994) A pore-forming protein with a metal-actuated switch. Protein Eng. 1994, 7, 655-62.

16. Krishnasastry, M., Walker, B., Braha, O., and Bayley, H. (1994) Surface labeling of key residues during the assembly of the transmembrane pore formed by staphylococcal α-hemolysin. FEBS Lett. 356, 66-71.