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Malini Raghavan

Biochemical and molecular interactions underlying immune recognition events


Associate Professor - Microbiology

Ph.D., Princeton

Dept:  Department of Microbiology and Immunology
Office Address:  6748 Med. Sci. II
Phone:  (734) 647-7752

Email:  malinir@umich.edu



The binding of complexes of peptides and major histocompatibility complex (MHC) class I molecules to T cell receptors is of fundamental importance for the recognition of virally infected cells by T cells. Our major interest is in the MHC class I antigen processing pathway, the cellular pathway by which complexes of peptides and MHC class I molecules are generated. We study specific components of this pathway, including the transporter associated with antigen processing (TAP), tapasin, and calreticulin. TAP transports peptides from the cytosol to the endoplasmic reticulum (ER) for binding to class I MHC molecules, and tapasin is an ER-resident protein that enhances peptide binding by MHC class I molecules. Calreticulin is a generic cellular chaperone in the ER.

Our goal is to understand the mechanism of function of these proteins at the biochemical and structural level. We use molecular biology and biochemical techniques to generate desired proteins in heterologous systems. We investigate mechanisms of function using biochemical and biophysical techniques.



Representative Publications

Rizvi, S. M., Mancino, L., Thammavongsa, V., Cantley, R. L and Raghavan , M., A polypeptide binding conformation of calreticulin is induced by heat-shock, calcium depletion, or by deletion of the C-terminal acidic domain. Mol. Cell, 2004, in press

Lapinski, P. E., Raghuraman, G., and Raghavan, M. Nucleotide interactions with membrane-bound transporter associated with antigen processing (TAP) proteins, J. Biol. Chem. 2003, in 278, 8229-8237, 2003.

Raghuraman, G., Lapinski P. E and Raghavan, M. Tapasin interacts with the membrane spanning domains of both TAP subunits and enhances the structural stability of TAP1/TAP2 complexes, J. Biol. Chem, 277, 41786-41794, 2002.

Mancino, L. , Rizvi. S. M., Lapinski, P. E and Raghavan, M. Calreticulin recognizes misfolded HLA-A2 heavy chains. Proc. Natl. Acad. Sci. USA, 99, 5931-5936, 2002

Arora, S. A. Lapinski, P. E. and Raghavan, M. The use of chimeric proteins to investigate the role of transporter associated with antigen processing structural domains in peptide binding and translocation. Proc. Natl. Acad. Sci USA, 98 , 7241-7246, 2001





      
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Last Updated: 8/10/2004
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