5c3t: Difference between revisions

Revision as of 07:18, 9 December 2015

PD-1 binding domain from human PD-L1

Structural highlights

5c3t is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4zqk
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[PD1L1_HUMAN] Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation and cytokine production.^[1] ^[2]

Publication Abstract from PubMed

Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has recently provided breakthrough progress in the treatment of melanoma, non-small cell lung cancer, and other types of cancer. Small-molecule drugs interfering with this pathway are highly awaited, but their development is hindered by insufficient structural information. This study reveals the molecular details of the human PD-1/PD-L1 interaction based on an X-ray structure of the complex. First, it is shown that the ligand binding to human PD-1 is associated with significant plasticity within the receptor. Second, a detailed molecular map of the interaction surface is provided, allowing definition of the regions within both interacting partners that may likely be targeted by small molecules.

Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1.,Zak KM, Kitel R, Przetocka S, Golik P, Guzik K, Musielak B, Domling A, Dubin G, Holak TA Structure. 2015 Oct 22. pii: S0969-2126(15)00402-5. doi:, 10.1016/j.str.2015.09.010. PMID:26602187^[3]

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

References

↑ Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999 Dec;5(12):1365-9. PMID:10581077 doi:10.1038/70932
↑ Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000 Oct 2;192(7):1027-34. PMID:11015443
↑ Zak KM, Kitel R, Przetocka S, Golik P, Guzik K, Musielak B, Domling A, Dubin G, Holak TA. Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1. Structure. 2015 Oct 22. pii: S0969-2126(15)00402-5. doi:, 10.1016/j.str.2015.09.010. PMID:26602187 doi:https://dx.doi.org/10.1016/j.str.2015.09.010

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OCA

[1] Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999 Dec;5(12):1365-9. PMID:10581077 doi:10.1038/70932

[2] Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000 Oct 2;192(7):1027-34. PMID:11015443

[3] Zak KM, Kitel R, Przetocka S, Golik P, Guzik K, Musielak B, Domling A, Dubin G, Holak TA. Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1. Structure. 2015 Oct 22. pii: S0969-2126(15)00402-5. doi:, 10.1016/j.str.2015.09.010. PMID:26602187 doi:https://dx.doi.org/10.1016/j.str.2015.09.010

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==PD-1 binding domain from human PD-L1==
+<StructureSection load='5c3t' size='340' side='right' caption='[[5c3t]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5c3t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C3T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C3T FirstGlance]. <br>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zqk|4zqk]]</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=5c3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c3t OCA], [http://pdbe.org/5c3t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c3t RCSB], [http://www.ebi.ac.uk/pdbsum/5c3t PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PD1L1_HUMAN PD1L1_HUMAN]] Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation and cytokine production.<ref>PMID:10581077</ref> <ref>PMID:11015443</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has recently provided breakthrough progress in the treatment of melanoma, non-small cell lung cancer, and other types of cancer. Small-molecule drugs interfering with this pathway are highly awaited, but their development is hindered by insufficient structural information. This study reveals the molecular details of the human PD-1/PD-L1 interaction based on an X-ray structure of the complex. First, it is shown that the ligand binding to human PD-1 is associated with significant plasticity within the receptor. Second, a detailed molecular map of the interaction surface is provided, allowing definition of the regions within both interacting partners that may likely be targeted by small molecules.
-The entry 5c3t is ON HOLD  until Paper Publication
+Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1.,Zak KM, Kitel R, Przetocka S, Golik P, Guzik K, Musielak B, Domling A, Dubin G, Holak TA Structure. 2015 Oct 22. pii: S0969-2126(15)00402-5. doi:, 10.1016/j.str.2015.09.010. PMID:26602187<ref>PMID:26602187</ref>
-Authors: Zak, K.M., Dubin, G., Holak, T.A.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description:
+<div class="pdbe-citations 5c3t" style="background-color:#fffaf0;"></div>
-[[Category: Unreleased Structures]]
+== References ==
-[[Category: Holak, T.A]]
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Dubin, G]]
-[[Category: Zak, K.M]]
+[[Category: Holak, T A]]
+[[Category: Zak, K M]]
+[[Category: Immune system]]
+[[Category: Immunology]]
+[[Category: Ligand]]
+[[Category: Pd1/pdl1 axis]]

5c3t: Difference between revisions

Revision as of 07:18, 9 December 2015

PD-1 binding domain from human PD-L1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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