This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

6hig

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

hPD-1/NBO1a Fab complex

Structural highlights

6hig is a 3 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	PDCD1, PD1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PDCD1_HUMAN] Systemic lupus erythematosus;Multiple sclerosis. Systemic lupus erythematosus 2 (SLEB2) [MIM:605218]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.^[1]

Function

[PDCD1_HUMAN] Inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. Possible cell death inducer, in association with other factors.^[2]

Publication Abstract from PubMed

Classical antagonistic antibodies (Abs) targeting PD-1, such as pembrolizumab and nivolumab, act through blockade of the PD-1-PDL-1 interaction. Here, we have identified novel antagonistic anti-PD-1 Abs not blocking the PD-1-PDL-1 interaction. The nonblocking Abs recognize epitopes on PD-1 located on the opposing face of the PDL-1 interaction and overlap with a newly identified evolutionarily conserved patch. These nonblocking Abs act predominantly through the CD28 coreceptor. Importantly, a combination of blocking and nonblocking Abs synergize in the functional recovery of antigen-specific exhausted CD8 T cells. Interestingly, nonblocking anti-PD-1 Abs have equivalent antitumor activity compared with blocker Abs in two mouse tumor models, and combination therapy using both classes of Abs enhanced tumor suppression in the mouse immunogenic tumor model. The identification of the novel nonblocker anti-PD-1 Abs and their synergy with classical blocker Abs may be instrumental in potentiating immunotherapy strategies and antitumor activity.

Tumor suppression of novel anti-PD-1 antibodies mediated through CD28 costimulatory pathway.,Fenwick C, Loredo-Varela JL, Joo V, Pellaton C, Farina A, Rajah N, Esteves-Leuenberger L, Decaillon T, Suffiotti M, Noto A, Ohmiti K, Gottardo R, Weissenhorn W, Pantaleo G J Exp Med. 2019 May 23. pii: jem.20182359. doi: 10.1084/jem.20182359. PMID:31123083^[3]

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

References

↑ Prokunina L, Castillejo-Lopez C, Oberg F, Gunnarsson I, Berg L, Magnusson V, Brookes AJ, Tentler D, Kristjansdottir H, Grondal G, Bolstad AI, Svenungsson E, Lundberg I, Sturfelt G, Jonssen A, Truedsson L, Lima G, Alcocer-Varela J, Jonsson R, Gyllensten UB, Harley JB, Alarcon-Segovia D, Steinsson K, Alarcon-Riquelme ME. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet. 2002 Dec;32(4):666-9. Epub 2002 Oct 28. PMID:12402038 doi:10.1038/ng1020
↑ Fife BT, Pauken KE. The role of the PD-1 pathway in autoimmunity and peripheral tolerance. Ann N Y Acad Sci. 2011 Jan;1217:45-59. doi: 10.1111/j.1749-6632.2010.05919.x. PMID:21276005 doi:10.1111/j.1749-6632.2010.05919.x
↑ Fenwick C, Loredo-Varela JL, Joo V, Pellaton C, Farina A, Rajah N, Esteves-Leuenberger L, Decaillon T, Suffiotti M, Noto A, Ohmiti K, Gottardo R, Weissenhorn W, Pantaleo G. Tumor suppression of novel anti-PD-1 antibodies mediated through CD28 costimulatory pathway. J Exp Med. 2019 May 23. pii: jem.20182359. doi: 10.1084/jem.20182359. PMID:31123083 doi:http://dx.doi.org/10.1084/jem.20182359

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6hig"

@@ Line 3: / Line 3: @@
 <StructureSection load='6hig' size='340' side='right'caption='[[6hig]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6hig]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HIG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HIG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6hig]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HIG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HIG 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=6hig FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hig OCA], [http://pdbe.org/6hig PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hig RCSB], [http://www.ebi.ac.uk/pdbsum/6hig PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hig ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDCD1, PD1 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6hig FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hig OCA], [http://pdbe.org/6hig PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hig RCSB], [http://www.ebi.ac.uk/pdbsum/6hig PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hig ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Fenwick, C]]
 [[Category: Loredo-Varela, J L]]

6hig

From Proteopedia

Current revision

hPD-1/NBO1a Fab complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox