Olson, Rich and Huey-Tubman, Kathryn E. and Dulac, Catherine and Bjorkman, Pamela J. (2005) Structure of a Pheromone Receptor-Associated MHC Molecule with an Open and Empty Groove. PLoS Biology, 3 (8). pp. 1436-1448. ISSN 1544-9173. http://resolver.caltech.edu/CaltechAUTHORS:OLSpb05
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Neurons in the murine vomeronasal organ (VNO) express a family of class Ib major histocompatibility complex (MHC) proteins (M10s) that interact with the V2R class of VNO receptors. This interaction may play a direct role in the detection of pheromonal cues that initiate reproductive and territorial behaviors. The crystal structure of M10.5, an M10 family member, is similar to that of classical MHC molecules. However, the M10.5 counterpart of the MHC peptide-binding groove is open and unoccupied, revealing the first structure of an empty class I MHC molecule. Similar to empty MHC molecules, but unlike peptide-filled MHC proteins and non-peptide–binding MHC homologs, M10.5 is thermally unstable, suggesting that its groove is normally occupied. However, M10.5 does not bind endogenous peptides when expressed in mammalian cells or when offered a mixture of class I–binding peptides. The F pocket side of the M10.5 groove is open, suggesting that ligands larger than 8–10-mer class I–binding peptides could fit by extending out of the groove. Moreover, variable residues point up from the groove helices, rather than toward the groove as in classical MHC structures. These data suggest that M10s are unlikely to provide specific recognition of class I MHC–binding peptides, but are consistent with binding to other ligands, including proteins such as the V2Rs.
|Additional Information:||Copyright: © 2005 Olson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Academic Editor: Andrej Sali, University of California, San Francisco, United States of America Received: April 6, 2005; Accepted: May 18, 2005; Published: July 12, 2005 Acknowledgments Protein sequencing analyses carried out by the Protein/Peptide Microanalytical Lab were supported by the Beckman Institute at the California Institute of Technology (Caltech). We thank Kyle Lassila and Heidi Privett for help with CD measurements, Tony Giannetti and Anthony West for help with Biacore experiments, Peter Snow, Inderjit Nangiana, and Cynthia Jones at the Caltech Protein Expression Center for assisting with insect cell expression, Fabio Papes for providing fractionated urine samples, the Ralph M.Parsons Foundation for computational support, and members of the Bjorkman laboratory for critical reading of the manuscript. This work was supported by a Rosalind Alcott Post-doctoral Fellowship administered by Caltech (R.O.), the Howard Hughes Medical Institute (C.D. and P.J.B.), and the NIH/NIDCD (R01 DC003903 (C.D.)). The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, Materials Sciences Division, of the U.S. Department of Energy under Contract No. DE-AC03-76SF00098 at Lawrence Berkeley National Laboratory. Portions of this research were carried out at the Stanford Synchrotron Radiation Laboratory, a national user facility operated by Stanford University on behalf of the U.S. Department of Energy, Office of Basic Energy Sciences. Competing interests. The authors have declared that no competing interests exist. Author contributions. RAO and PJB conceived and designed the experiments. RAO and KEHT performed the experiments. RAO, KEHT, CD, and PJB analyzed the data. CD and PJB contributed reagents/materials/analysis tools. RAO, CD, and PJB wrote the paper.|
|Official Citation:||Olson R, Huey-Tubman KE, Dulac C, Bjorkman PJ (2005) Structure of a Pheromone Receptor-Associated MHC Molecule with an Open and Empty Groove. PLoS Biol 3(8): e257|
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|Deposited On:||30 Sep 2005|
|Last Modified:||26 Dec 2012 08:41|
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