SMRL: Stanford NMR Facility and Resource

Cochran Group Research at the SMRL

K. Christopher Garcia

Associate Professor
Dept. of Molecular & Cellular Physiology
Dept. of Structural Biology

kcgarcia at

Group Web Page


Varani L, Bankovich AJ, Liu CW, Colf LA, Jones LL, Kranz DM, Puglisi JD, Garcia KC (2007) "Solution mapping of T cell receptor docking footprints on peptide-MHC" Proc Natl Acad Sci U S A 104 13080-5. PDF

(Details Below) Hanick NA, Rickert M, Varani L, Bankovich AJ, Cochran JR, Kim DM, Surh CD, Garcia KC (2007) "Elucidation of the interleukin-15 binding site on its alpha receptor by NMR" Biochemistry 46 9453-61. PDF


Elucidation of the interleukin-15 binding site on its alpha receptor by NMR

Hanick NA, Rickert M, Varani L, Bankovich AJ, Cochran JR, Kim DM, Surh CD, Garcia KC (2007) Biochemistry 46 9453-61. PDF

Abstract: The cytokine interleukin-15 (IL-15) signals through the formation of a quaternary receptor complex composed of an IL-15-specific alpha receptor, together with beta and gammac receptors that are shared with interleukin-2 (IL-2). The initiating step in the formation of this signaling complex is the interaction between IL-15 and IL-15Ralpha, which is a single sushi domain bearing strong structural homology to one of the two sushi domains of IL-2Ralpha. The crystal structure of the IL2-Ralpha/IL-2 complex has been determined, however little is known about the analogous IL-15Ralpha/IL-15 binding interaction. Here we show that recombinant IL-15 can be overexpressed as a stable complex in the presence of its high affinity receptor, IL-15Ralpha. We find that this complex is 10-fold more active than IL-15 alone in stimulating proliferation and survival of memory phenotype CD8 T cells. To probe the ligand/receptor interface, we used solution NMR to map chemical shifts on 15N-labeled IL-15Ralpha in complex with unlabeled IL-15. Our results predict that the binding surface on IL-15Ralpha involves strands C and D, similar to IL-2Ralpha. The interface, as predicted here, leaves open the possibility of trans-presentation of IL-15 by IL-15Ralpha on an opposing cell.

Figure Caption. Chemical shifts mapped on to IL-15Ralpha NMR structure and comparison to contacts derived from the crystal structure of IL-2/ IL-2Ralpha. Residues with significant chemical shift differences were mapped onto a ribbon representation of the IL-15Ralpha NMR structure (A, magenta). IL-2Ralpha from the IL-2 crystal structure is shown with residues that are in direct contact with IL-2 in magenta (B). Molecular surface representations of IL-15Ralpha with chemical shift mapping results depicted as magenta surface area (C) and IL-2Ralpha with contact residues as magenta surface area and IL-2 (purple) bound (D).
Bio-X Structural Biology School of Medicine Stanford University
© Stanford University, All Rights Reserved.