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Biochemical characterization of the LAG-3 protein

Zarixia Zavala, Ph.D.

zzavala@uprm.edu, Q-372J, x2519

Research Interests

The adaptive immune response depends on the specific recognition by a T-cell receptor of an antigenic peptide bound to a major histocompatibility complex (MHC) molecule (MHC-pep), as well as interaction of this same MHC-pep with a co-receptor molecule like the CD4 protein.  Activation of the T-cell response is accompanied by the modification of the expression of several genes that encode molecules involved in T-cell proliferation, effector functions and cell-cell interaction.  The lymphocyte activation gene-3 is one of them; this gene produces a protein that plays an important role in negatively regulating T-cell activation and proliferation. 

Our lab is interested in characterizing the LAG-3 protein and its interaction with class II MHC proteins using crystallography, cell biology and biochemical methods, like gel filtration, dynamic light scattering, surface plasmon resonance, and analytical ultracentrifugation.  A detailed understanding of the biochemical mechanisms of the LAG-3: MHC II interaction will contribute to our understanding of T-cell regulation and lay the foundation for the development of novel strategies for regulating T-cell responses.

Publications:

Zavala-Ruiz, Z., Strug, I., Anderson, M.W., Gorski, J. and Stern, L.J.  Side-chain specificity at the P10 position of the peptide binding site of a class II MHC protein.  Chem. Biol. Oct. 2004 11(10):1395-1402.

Zavala-Ruiz, Z., Strug, I., Walker, B.D., Norris, P.J., and Stern, L.J. A hairpin turn in a MHC-bound peptide orients residues outside the binding groove for T-cell recognition Proc Natl Acad Sci U S A. 2004 Sept 7;101(36):13279-84.

Zavala-Ruiz, Z., Sundberg, E.J., Stone, J.D., DeOliveira, D.B., Chan, I.C., Svendsen, J., Mariuzza, R.A., and Stern, L.J. Exploration of the P6/P7 region of the peptide-binding site of the human class II MHC protein, HLA-DR1. J Biol Chem. 2003 Nov 7;278(45):44904-44912.

Zarutskie, J.A., Busch R., Zavala-Ruiz, Z, Rushe, M, Mellins, E.D., and Stern, L.J. The kinetic basis of peptide exchange catalysis by HLA-DM.  Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12450-5.

Aster, J.C., Simms W.B., Zavala-Ruiz, Z, Patriub, V,  Blacklow, S.C.The folding and structural integrity of the first LIN-12 module of human Notch1 are calcium-dependent.    Biochemistry. 1999 Apr 13;38(15): 4736-42.