6v67: Difference between revisions

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<StructureSection load='6v67' size='340' side='right'caption='[[6v67]], [[Resolution|resolution]] 1.07&Aring;' scene=''>
<StructureSection load='6v67' size='340' side='right'caption='[[6v67]], [[Resolution|resolution]] 1.07&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6v67]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V67 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V67 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6v67]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V67 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V67 FirstGlance]. <br>
</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=6v67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v67 OCA], [https://pdbe.org/6v67 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v67 RCSB], [https://www.ebi.ac.uk/pdbsum/6v67 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v67 ProSAT]</span></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]] 1.07&#8491;</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=6v67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v67 OCA], [https://pdbe.org/6v67 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v67 RCSB], [https://www.ebi.ac.uk/pdbsum/6v67 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v67 ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Programmed cell death protein-1 (PD-1) expressed on activated T cells inhibits T cell function and proliferation to prevent an excessive immune response, and disease can result if this delicate balance is shifted in either direction. Tumor cells often take advantage of this pathway by overexpressing the PD-1 ligand PD-L1 to evade destruction by the immune system. Alternatively, if there is a decrease in function of the PD-1 pathway, unchecked activation of the immune system and autoimmunity can result. Using a combination of computation and experiment, we designed a hyperstable 40-residue miniprotein, PD-MP1, that specifically binds murine and human PD-1 at the PD-L1 interface with a Kd of approximately 100 nM. The apo crystal structure shows that the binder folds as designed with a backbone RMSD of 1.3 A to the design model. Trimerization of PD-MP1 resulted in a PD-1 agonist that strongly inhibits murine T cell activation. This small, hyperstable PD-1 binding protein was computationally designed with an all-beta interface, and the trimeric agonist could contribute to treatments for autoimmune and inflammatory diseases.
Computational design of a synthetic PD-1 agonist.,Bryan CM, Rocklin GJ, Bick MJ, Ford A, Majri-Morrison S, Kroll AV, Miller CJ, Carter L, Goreshnik I, Kang A, DiMaio F, Tarbell KV, Baker D Proc Natl Acad Sci U S A. 2021 Jul 20;118(29). pii: 2102164118. doi:, 10.1073/pnas.2102164118. PMID:34272285<ref>PMID:34272285</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6v67" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Synthetic construct sequences]]
[[Category: Synthetic construct]]
[[Category: Baker, D]]
[[Category: Baker D]]
[[Category: Bick, M J]]
[[Category: Bick MJ]]
[[Category: Bryan, C M]]
[[Category: Bryan CM]]
[[Category: Dimaio, F]]
[[Category: Dimaio F]]
[[Category: Kang, A]]
[[Category: Kang A]]
[[Category: Binder]]
[[Category: Computational design]]
[[Category: De novo protein]]
[[Category: Disulfide miniprotein]]
[[Category: Pd-1]]

Revision as of 07:09, 3 April 2024

Apo Structure of the De Novo PD-1 Binding Miniprotein GR918.2

6v67, resolution 1.07Å

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