View source for 6ewo


==Crystal structure of non-phosphorylated form of RTF PHOSPHOPEPTIDE BOUND TO HLA-A2 in complex with LILRB1==
<StructureSection load='6ewo' size='340' side='right' caption='[[6ewo]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ewo]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EWO FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ewo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ewo OCA], [http://pdbe.org/6ewo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ewo RCSB], [http://www.ebi.ac.uk/pdbsum/6ewo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ewo ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref>   Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/1A02_HUMAN 1A02_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/SYNEM_HUMAN SYNEM_HUMAN]] Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteropolymeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteropolymeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells.<ref>PMID:11353857</ref> <ref>PMID:16777071</ref> <ref>PMID:18028034</ref>  [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
X-ray crystallographic studies of class I peptide-MHC molecules (pMHC) continue to provide important insights into immune recognition, however their success depends on generation of diffraction-quality crystals, which remains a significant challenge. While protein engineering techniques such as surface-entropy reduction and lysine methylation have proven utility in facilitating and/or improving protein crystallisation, they risk affecting the conformation and biochemistry of the class I MHC antigen binding groove. An attractive alternative is the use of noncovalent crystallisation chaperones, however these have not been developed for pMHC. Here we describe a method for promoting class I pMHC crystallisation, by exploiting its natural ligand interaction with the immunoregulatory receptor LILRB1 as a novel crystallisation chaperone. First, focussing on a model HIV-1-derived HLA-A2-restricted peptide, we determined a 2.4A HLA-A2/LILRB1 structure, which validated that co-crystallisation with LILRB1 does not alter conformation of the antigenic peptide. We then demonstrated that addition of LILRB1 enhanced the crystallisation of multiple peptide-HLA-A2 complexes, and identified a generic condition for initial co-crystallisation. LILRB1 chaperone-based crystallisation enabled structure determination for HLA-A2 complexes previously intransigent to crystallisation, including both conventional and post-translationally-modified peptides, of diverse lengths. Since both the LILRB1 recognition interface on the HLA-A2 alpha3 domain molecule and HLA-A2-mediated crystal contacts are predominantly conserved across class I MHC molecules, the approach we outline could prove applicable to a diverse range of class I pMHC. LILRB1 chaperone-mediated crystallisation should expedite molecular insights into the immunobiology of diverse immune-related diseases and immunotherapeutic strategies, particularly involving class I pMHC complexes that are challenging to crystallise.

Application of the immunoregulatory receptor LILRB1 as a crystallisation chaperone for human class I MHC complexes.,Mohammed F, Stones DH, Willcox BE J Immunol Methods. 2018 Oct 24. pii: S0022-1759(18)30250-3. doi:, 10.1016/j.jim.2018.10.011. PMID:30365927<ref>PMID:30365927</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ewo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Mohammed, F]]
[[Category: Stones, D H]]
[[Category: Willcox, B E]]
[[Category: Crystallisation chaperone]]
[[Category: Hla-a2]]
[[Category: Immune system]]
[[Category: Lilrb1]]
[[Category: Nonphosphopeptide]]
[[Category: Peptide-mhc complex]]
[[Category: Tumour antigen]]