6y07 | pdb_00006y07

Designing a Granulopoietic Protein by Topological Rescaffolding 1: Sohair

spinqualitylabelsall models 6y07, 19 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6y07 is a 1 chain structure with sequence from Synthetic construct sequences. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Computational protein design is rapidly becoming more powerful, and improving the accuracy of computational methods would greatly streamline protein engineering by eliminating the need for empirical optimization in the laboratory. In this work, we set out to design novel granulopoietic agents using a rescaffolding strategy with the goal of achieving simpler and more stable proteins. All of the 4 experimentally tested designs were folded, monomeric, and stable, while the 2 determined structures agreed with the design models within less than 2.5 A. Despite the lack of significant topological or sequence similarity to their natural granulopoietic counterpart, 2 designs bound to the granulocyte colony-stimulating factor (G-CSF) receptor and exhibited potent, but delayed, in vitro proliferative activity in a G-CSF-dependent cell line. Interestingly, the designs also induced proliferation and differentiation of primary human hematopoietic stem cells into mature granulocytes, highlighting the utility of our approach to develop highly active therapeutic leads purely based on computational design. Design of novel granulopoietic proteins by topological rescaffolding.,Hernandez Alvarez B, Skokowa J, Coles M, Mir P, Nasri M, Maksymenko K, Weidmann L, Rogers KW, Welte K, Lupas AN, Muller P, ElGamacy M PLoS Biol. 2020 Dec 22;18(12):e3000919. doi: 10.1371/journal.pbio.3000919., eCollection 2020 Dec. PMID:33351791 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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