HOMOLOGY MODELS FOR THE PERB11 MULTIGENE FAMILY

Background: PERB11 is a multicopy polymorphic gene family found in ass ociation with HLA Class I genes within the major histocompatibility co mplex (MHC). Although its function is unknown, PERB11 has sequence sim ilarities to HLA Class I and other related proteins. To explore the po ssible functional roles for PERB11, homology models have been construc ted-using both HLA Class I and Class I-like protein structures as temp lates. Results: The models show that PERB11.1 appears to have an unusu al distribution of charged residues that potentially give the molecule a distinct polarity. Furthermore, a cluster of negatively charged res idues in the traditional P2 site may form a novel binding site for a p ositively charged ligand such as a metal ion or complex. Other charged residues line the floor and walls of the cleft and are able to form s alt bridges, reminiscent of the closed cleft of the Class I-like mouse neonatal Fc receptor structure. The closely related PERB11.2 family h as a different arrangement of charged residues in the cleft, but these residues are still able to form salt bridges. Unlike HLA Class I, the majority of polymorphic positions in the PERB11 family occur outside the cleft and on the surface of the molecule. Conclusions: Homology mo dels for PERB11 suggest that the structure is capable of associating w ith beta 2 microglobulin or a similar molecule. Furthermore, not all o f the potential glycosylation sites suggested by the PERB11 sequences appear viable. Importantly, the models suggest that the molecule has a less accessible cleft than HLA Class I and is not, therefore, able to bind peptides. Other small ligands, including metal ions, might be bo und, however.