5mgt

From Proteopedia

(Difference between revisions)

Revision as of 07:40, 8 March 2023

Complex of human NKR-P1 and LLT1 in deglycosylated forms

Structural highlights

5mgt is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CLC2D_HUMAN Receptor for KLRB1 that protects target cells against natural killer cell-mediated lysis. Inhibits osteoclast formation. Inhibits bone resorption. Modulates the release of interferon-gamma. Binds high molecular weight sulfated glycosaminoglycans.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Signaling by the human C-type lectin-like receptor, natural killer (NK) cell inhibitory receptor NKR-P1, has a critical role in many immune-related diseases and cancer. C-type lectin-like receptors have weak affinities to their ligands; therefore, setting up a comprehensive model of NKR-P1-LLT1 interactions that considers the natural state of the receptor on the cell surface is necessary to understand its functions. Here we report the crystal structures of the NKR-P1 and NKR-P1:LLT1 complexes, which provides evidence that NKR-P1 forms homodimers in an unexpected arrangement to enable LLT1 binding in two modes, bridging two LLT1 molecules. These interaction clusters are suggestive of an inhibitory immune synapse. By observing the formation of these clusters in solution using SEC-SAXS analysis, by dSTORM super-resolution microscopy on the cell surface, and by following their role in receptor signaling with freshly isolated NK cells, we show that only the ligation of both LLT1 binding interfaces leads to effective NKR-P1 inhibitory signaling. In summary, our findings collectively support a model of NKR-P1:LLT1 clustering, which allows the interacting proteins to overcome weak ligand-receptor affinity and to trigger signal transduction upon cellular contact in the immune synapse.

Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse.,Blaha J, Skalova T, Kalouskova B, Skorepa O, Cmunt D, Grobarova V, Pazicky S, Polachova E, Abreu C, Stransky J, Koval T, Duskova J, Zhao Y, Harlos K, Hasek J, Dohnalek J, Vanek O Nat Commun. 2022 Aug 26;13(1):5022. doi: 10.1038/s41467-022-32577-6. PMID:36028489^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hu YS, Zhou H, Myers D, Quinn JM, Atkins GJ, Ly C, Gange C, Kartsogiannis V, Elliott J, Kostakis P, Zannettino AC, Cromer B, McKinstry WJ, Findlay DM, Gillespie MT, Ng KW. Isolation of a human homolog of osteoclast inhibitory lectin that inhibits the formation and function of osteoclasts. J Bone Miner Res. 2004 Jan;19(1):89-99. PMID:14753741 doi:http://dx.doi.org/10.1359/JBMR.0301215
↑ Mathew PA, Chuang SS, Vaidya SV, Kumaresan PR, Boles KS, Pham HT. The LLT1 receptor induces IFN-gamma production by human natural killer cells. Mol Immunol. 2004 Mar;40(16):1157-63. PMID:15104121
↑ Rosen DB, Bettadapura J, Alsharifi M, Mathew PA, Warren HS, Lanier LL. Cutting edge: lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A receptor. J Immunol. 2005 Dec 15;175(12):7796-9. PMID:16339513
↑ Bláha J, Skálová T, Kalousková B, Skořepa O, Cmunt D, Grobárová V, Pazicky S, Poláchová E, Abreu C, Stránský J, Kovaľ T, Dušková J, Zhao Y, Harlos K, Hašek J, Dohnálek J, Vaněk O. Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse. Nat Commun. 2022 Aug 26;13(1):5022. PMID:36028489 doi:10.1038/s41467-022-32577-6

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5mgt"

@@ Line 3: / Line 3: @@
 <StructureSection load='5mgt' size='340' side='right'caption='[[5mgt]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5mgt]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MGT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MGT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5mgt]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MGT FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CLEC2D, CLAX, LLT1, OCIL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), KLRB1, CLEC5B, NKRP1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5mgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgt OCA], [https://pdbe.org/5mgt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mgt RCSB], [https://www.ebi.ac.uk/pdbsum/5mgt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgt ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgt OCA], [http://pdbe.org/5mgt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mgt RCSB], [http://www.ebi.ac.uk/pdbsum/5mgt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgt ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CLC2D_HUMAN CLC2D_HUMAN]] Receptor for KLRB1 that protects target cells against natural killer cell-mediated lysis. Inhibits osteoclast formation. Inhibits bone resorption. Modulates the release of interferon-gamma. Binds high molecular weight sulfated glycosaminoglycans.<ref>PMID:14753741</ref> <ref>PMID:15104121</ref> <ref>PMID:16339513</ref>  [[http://www.uniprot.org/uniprot/KLRB1_HUMAN KLRB1_HUMAN]] Plays an inhibitory role on natural killer (NK) cells cytotoxicity. Activation results in specific acid sphingomyelinase/SMPD1 stimulation with subsequent marked elevation of intracellular ceramide. Activation also leads to AKT1/PKB and RPS6KA1/RSK1 kinases stimulation as well as markedly enhanced T-cell proliferation induced by anti-CD3. Acts as a lectin that binds to the terminal carbohydrate Gal-alpha(1,3)Gal epitope as well as to the N-acetyllactosamine epitope. Binds also to CLEC2D/LLT1 as a ligand and inhibits NK cell-mediated cytotoxicity as well as interferon-gamma secretion in target cells.<ref>PMID:16455998</ref> <ref>PMID:16925668</ref> <ref>PMID:8077657</ref>
+[https://www.uniprot.org/uniprot/CLC2D_HUMAN CLC2D_HUMAN] Receptor for KLRB1 that protects target cells against natural killer cell-mediated lysis. Inhibits osteoclast formation. Inhibits bone resorption. Modulates the release of interferon-gamma. Binds high molecular weight sulfated glycosaminoglycans.<ref>PMID:14753741</ref> <ref>PMID:15104121</ref> <ref>PMID:16339513</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Signaling by the human C-type lectin-like receptor, natural killer (NK) cell inhibitory receptor NKR-P1, has a critical role in many immune-related diseases and cancer. C-type lectin-like receptors have weak affinities to their ligands; therefore, setting up a comprehensive model of NKR-P1-LLT1 interactions that considers the natural state of the receptor on the cell surface is necessary to understand its functions. Here we report the crystal structures of the NKR-P1 and NKR-P1:LLT1 complexes, which provides evidence that NKR-P1 forms homodimers in an unexpected arrangement to enable LLT1 binding in two modes, bridging two LLT1 molecules. These interaction clusters are suggestive of an inhibitory immune synapse. By observing the formation of these clusters in solution using SEC-SAXS analysis, by dSTORM super-resolution microscopy on the cell surface, and by following their role in receptor signaling with freshly isolated NK cells, we show that only the ligation of both LLT1 binding interfaces leads to effective NKR-P1 inhibitory signaling. In summary, our findings collectively support a model of NKR-P1:LLT1 clustering, which allows the interacting proteins to overcome weak ligand-receptor affinity and to trigger signal transduction upon cellular contact in the immune synapse.
+Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse.,Blaha J, Skalova T, Kalouskova B, Skorepa O, Cmunt D, Grobarova V, Pazicky S, Polachova E, Abreu C, Stransky J, Koval T, Duskova J, Zhao Y, Harlos K, Hasek J, Dohnalek J, Vanek O Nat Commun. 2022 Aug 26;13(1):5022. doi: 10.1038/s41467-022-32577-6. PMID:36028489<ref>PMID:36028489</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 5mgt" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Blaha, J]]
+[[Category: Blaha J]]
-[[Category: Dohnalek, J]]
+[[Category: Dohnalek J]]
-[[Category: Harlos, K]]
+[[Category: Harlos K]]
-[[Category: Hasek, J]]
+[[Category: Hasek J]]
-[[Category: Koval, T]]
+[[Category: Koval T]]
-[[Category: Skalova, T]]
+[[Category: Skalova T]]
-[[Category: Stransky, J]]
+[[Category: Stransky J]]
-[[Category: Vanek, O]]
+[[Category: Vanek O]]
-[[Category: Yuguang, Z]]
+[[Category: Yuguang Z]]
-[[Category: Ctl fold]]
-[[Category: Immune system]]
-[[Category: Natural killer cell]]
-[[Category: Receptor]]
-[[Category: Receptor-ligand complex]]

5mgt

From Proteopedia

Revision as of 07:40, 8 March 2023

Complex of human NKR-P1 and LLT1 in deglycosylated forms

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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