The Structure of the Atypical Killer Cell Immunoglobulin-like Receptor, KIR2DL4
| Autor: | Corinne R Hitchen, Phillip Pymm, Richard Berry, Matthew C.J. Wilce, Shoeib Moradi, Julian P. Vivian, Hugh H. Reid, Simone A. Beckham, Jamie Rossjohn, Nicholas G Walpole, Matthew A. Perugini, Craig Steven Clements, Andrew G. Brooks |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Stereochemistry Immunology Molecular Sequence Data Killer-cell immunoglobulin-like receptor Gene Expression chemical and pharmacologic phenomena Immunoglobulin domain Moths Biology Crystallography X-Ray Biochemistry Protein Structure Secondary KIR2DL4 Protein structure Tetramer immune system diseases HLA-G otorhinolaryngologic diseases Escherichia coli HLA-B Antigens Animals Amino Acid Sequence Cloning Molecular Molecular Biology HLA-G Antigens hemic and immune systems Cell Biology Recombinant Proteins Protein Structure Tertiary Cell biology Receptors KIR2DL4 embryonic structures Protein Multimerization KIR3DL1 Baculoviridae Sequence Alignment |
| Zdroj: | Journal of Biological Chemistry. 290:10460-10471 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m114.612291 |
| Popis: | The engagement of natural killer cell immunoglobulin-like receptors (KIRs) with their target ligands, human leukocyte antigen (HLA) molecules, is a critical component of innate immunity. Structurally, KIRs typically have either two (D1-D2) or three (D0-D1-D2) extracellular immunoglobulin domains, with the D1 and D2 domain recognizing the α1 and α2 helices of HLA, respectively, whereas the D0 domain of the KIR3DLs binds a loop region flanking the α1 helix of the HLA molecule. KIR2DL4 is distinct from other KIRs (except KIR2DL5) in that it does not contain a D1 domain and instead has a D0-D2 arrangement. Functionally, KIR2DL4 is also atypical in that, unlike all other KIRs, KIR2DL4 has both activating and inhibitory signaling domains. Here, we determined the 2.8 Å crystal structure of the extracellular domains of KIR2DL4. Structurally, KIR2DL4 is reminiscent of other KIR2DL receptors, with the D0 and D2 adopting the C2-type immunoglobulin fold arranged with an acute elbow angle. However, KIR2DL4 self-associated via the D0 domain in a concentration-dependent manner and was observed as a tetramer in the crystal lattice by size exclusion chromatography, dynamic light scattering, analytical ultracentrifugation, and small angle x-ray scattering experiments. The assignment of residues in the D0 domain to forming the KIR2DL4 tetramer precludes an interaction with HLA akin to that observed for KIR3DL1. Accordingly, no interaction was observed to HLA by direct binding studies. Our data suggest that the unique functional properties of KIR2DL4 may be mediated by self-association of the receptor. |
| Databáze: | OpenAIRE |
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