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7ny0
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7ny0 is ON HOLD Authors: ElGamacy, M., Coles, M. Description: Solution structure of Boskar4; a de novo designed G-CSF agonist [[Category: Unrelease...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Solution structure of Boskar4; a de novo designed G-CSF agonist== | |
| + | <StructureSection load='7ny0' size='340' side='right'caption='[[7ny0]], [[NMR_Ensembles_of_Models | 17 NMR models]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7ny0]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NY0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NY0 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=7ny0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ny0 OCA], [https://pdbe.org/7ny0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ny0 RCSB], [https://www.ebi.ac.uk/pdbsum/7ny0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ny0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Protein therapeutics frequently face major challenges, including complicated production, instability, poor solubility, and aggregation. De novo protein design can readily address these challenges. Here, we demonstrate the utility of a topological refactoring strategy to design novel granulopoietic proteins starting from the granulocyte-colony stimulating factor (G-CSF) structure. We change a protein fold by rearranging the sequence and optimising it towards the new fold. Testing four designs, we obtain two that possess nanomolar activity, the most active of which is highly thermostable and protease-resistant, and matches its designed structure to atomic accuracy. While the designs possess starkly different sequence and structure from the native G-CSF, they show specific activity in differentiating primary human haematopoietic stem cells into mature neutrophils. The designs also show significant and specific activity in vivo. Our topological refactoring approach is largely independent of sequence or structural context, and is therefore applicable to a wide range of protein targets. | ||
| - | + | A topological refactoring design strategy yields highly stable granulopoietic proteins.,Skokowa J, Hernandez Alvarez B, Coles M, Ritter M, Nasri M, Haaf J, Aghaallaei N, Xu Y, Mir P, Krahl AC, Rogers KW, Maksymenko K, Bajoghli B, Welte K, Lupas AN, Muller P, ElGamacy M Nat Commun. 2022 May 26;13(1):2948. doi: 10.1038/s41467-022-30157-2. PMID:35618709<ref>PMID:35618709</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7ny0" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Coles, M]] | [[Category: Coles, M]] | ||
| - | [[Category: | + | [[Category: ElGamacy, M]] |
| + | [[Category: De novo protein]] | ||
| + | [[Category: Four-helix bundle]] | ||
| + | [[Category: G-csf agonist]] | ||
| + | [[Category: Protein design]] | ||
Current revision
Solution structure of Boskar4; a de novo designed G-CSF agonist
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