5c9j

From Proteopedia

(Difference between revisions)

Current revision

Human CD1c with ligands in A' and F' channel

Structural highlights

5c9j is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CD1C_HUMAN Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.^[1] ^[2] ^[3] ^[4] CD1B_HUMAN Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.^[5] ^[6]

Publication Abstract from PubMed

Cluster of differentiation 1c (CD1c)-dependent self-reactive T cells are abundant in human blood, but self-antigens presented by CD1c to the T-cell receptors of these cells are poorly understood. Here we present a crystal structure of CD1c determined at 2.4 A revealing an extended ligand binding potential of the antigen groove and a substantially different conformation compared with known CD1c structures. Computational simulations exploring different occupancy states of the groove reenacted these different CD1c conformations and suggested cholesteryl esters (CE) and acylated steryl glycosides (ASG) as new ligand classes for CD1c. Confirming this, we show that binding of CE and ASG to CD1c enables the binding of human CD1c self-reactive T-cell receptors. Hence, human CD1c adopts different conformations dependent on ligand occupancy of its groove, with CE and ASG stabilizing CD1c conformations that provide a footprint for binding of CD1c self-reactive T-cell receptors.

Cholesteryl esters stabilize human CD1c conformations for recognition by self-reactive T cells.,Mansour S, Tocheva AS, Cave-Ayland C, Machelett MM, Sander B, Lissin NM, Molloy PE, Baird MS, Stubs G, Schroder NW, Schumann RR, Rademann J, Postle AD, Jakobsen BK, Marshall BG, Gosain R, Elkington PT, Elliott T, Skylaris CK, Essex JW, Tews I, Gadola SD Proc Natl Acad Sci U S A. 2016 Feb 16. pii: 201519246. PMID:26884207^[7]

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

References

↑ Moody DB, Ulrichs T, Muhlecker W, Young DC, Gurcha SS, Grant E, Rosat JP, Brenner MB, Costello CE, Besra GS, Porcelli SA. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature. 2000 Apr 20;404(6780):884-8. PMID:10786796 doi:http://dx.doi.org/10.1038/35009119
↑ Sugita M, van Der Wel N, Rogers RA, Peters PJ, Brenner MB. CD1c molecules broadly survey the endocytic system. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8445-50. PMID:10890914 doi:http://dx.doi.org/10.1073/pnas.150236797
↑ Briken V, Jackman RM, Watts GF, Rogers RA, Porcelli SA. Human CD1b and CD1c isoforms survey different intracellular compartments for the presentation of microbial lipid antigens. J Exp Med. 2000 Jul 17;192(2):281-8. PMID:10899914
↑ Scharf L, Li NS, Hawk AJ, Garzon D, Zhang T, Fox LM, Kazen AR, Shah S, Haddadian EJ, Gumperz JE, Saghatelian A, Faraldo-Gomez JD, Meredith SC, Piccirilli JA, Adams EJ. The 2.5 a structure of CD1c in complex with a mycobacterial lipid reveals an open groove ideally suited for diverse antigen presentation. Immunity. 2010 Dec 14;33(6):853-62. PMID:21167756 doi:10.1016/j.immuni.2010.11.026
↑ Shamshiev A, Donda A, Prigozy TI, Mori L, Chigorno V, Benedict CA, Kappos L, Sonnino S, Kronenberg M, De Libero G. The alphabeta T cell response to self-glycolipids shows a novel mechanism of CD1b loading and a requirement for complex oligosaccharides. Immunity. 2000 Aug;13(2):255-64. PMID:10981968
↑ Winau F, Schwierzeck V, Hurwitz R, Remmel N, Sieling PA, Modlin RL, Porcelli SA, Brinkmann V, Sugita M, Sandhoff K, Kaufmann SH, Schaible UE. Saposin C is required for lipid presentation by human CD1b. Nat Immunol. 2004 Feb;5(2):169-74. Epub 2004 Jan 11. PMID:14716313 doi:10.1038/ni1035
↑ Mansour S, Tocheva AS, Cave-Ayland C, Machelett MM, Sander B, Lissin NM, Molloy PE, Baird MS, Stubs G, Schroder NW, Schumann RR, Rademann J, Postle AD, Jakobsen BK, Marshall BG, Gosain R, Elkington PT, Elliott T, Skylaris CK, Essex JW, Tews I, Gadola SD. Cholesteryl esters stabilize human CD1c conformations for recognition by self-reactive T cells. Proc Natl Acad Sci U S A. 2016 Feb 16. pii: 201519246. PMID:26884207 doi:http://dx.doi.org/10.1073/pnas.1519246113

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5c9j"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5c9j]] is a 2 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=5C9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C9J FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=STE:STEARIC+ACID'>STE</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=STE:STEARIC+ACID'>STE</scene></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=5c9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c9j OCA], [https://pdbe.org/5c9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c9j RCSB], [https://www.ebi.ac.uk/pdbsum/5c9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c9j ProSAT]</span></td></tr>
 </table>

5c9j

From Proteopedia

Current revision

Human CD1c with ligands in A' and F' channel

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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