2gw5
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Crystal Structure of LIR-2 (ILT4) at 1.8 : differences from LIR-1 (ILT2) in regions implicated in the binding of the Cytomegalovirus class I MHC homolog UL18
OverviewOverview
BACKGROUND: Leukocyte Immunoglobulin-like Receptor-1 (LIR-1) and LIR-2, (also known as ILT2 and ILT4 respectively) are highly related cell surface, receptors that bind a broad range of class I MHC molecules with low, (microM) affinities. Expressed on monocytic cells and macrophages, both, molecules transmit inhibitory signals after binding ligands. In addition, to binding host class I MHC, the LIR-1 molecule, which is also expressed, on lymphoid tissues, binds with a high (nM) affinity to UL18, a class I, MHC homolog encoded by Human Cytomegalovirus (HCMV). In comparison, LIR-2, binds UL18 only weakly (microM KD). To understand how HCMV preferentially, targets the more broadly expressed LIR-1 molecule, we determined the, crystal structure of a ligand-binding fragment of LIR-2, and compared this, to the existing high-resolution crystal structure of LIR-1. RESULTS:, Recombinant LIR-2 (domains 1 and 2) was produced in E. coli and, crystallized using streak seeding to optimize the crystal morphology. A, data set complete to 1.8 A was collected at 100 K from a single crystal in, the P4(1)2(1)2 spacegroup. The structure was solved by molecular, replacement, using a search model based on the LIR-1 structure., CONCLUSIONS: The overall structure of LIR-2 D1D2 resembles both LIR-1, and, Killer Inhibitory Receptors, in that the A strand in each domain forms, hydrogen bonds to both beta sheets, and there is a sharp angle between the, two immunoglobulin-like domains. However, differences from LIR-1 are, observed in each domain, with two key changes apparent in the, ligand-binding domain, D1. The region corresponding to the residue 44-57, helix of LIR-1 adopts a topology distinct from that of both LIR-1 and the, KIR structures, involving a shortened 310 helix. Secondly, the predicted, UL18 binding region of LIR-1 is altered substantially in LIR-2: the 76-84, loop mainchain is displaced 11 A with respect to LIR-1, and Tyrosine 38, adopts an alternative rotamer conformation. In summary, the structure of, LIR-2 has revealed significant differences to LIR-1, including ones that, may help to explain the >1000-fold lower affinity of LIR-2 for UL18.
About this StructureAbout this Structure
2GW5 is a Single protein structure of sequence from Homo sapiens with IPA as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of LIR-2 (ILT4) at 1.8 A: differences from LIR-1 (ILT2) in regions implicated in the binding of the Human Cytomegalovirus class I MHC homolog UL18., Willcox BE, Thomas LM, Chapman TL, Heikema AP, West AP Jr, Bjorkman PJ, BMC Struct Biol. 2002 Oct 11;2:6. PMID:12390682
Page seeded by OCA on Mon Nov 12 22:23:18 2007