Structural highlights
Publication Abstract from PubMedIn natural proteins, structured loops have central roles in molecular recognition, signal transduction and enzyme catalysis. However, because of the intrinsic flexibility and irregularity of loop regions, organizing multiple structured loops at protein functional sites has been very difficult to achieve by de novo protein design. Here we describe a solution to this problem that designs tandem repeat proteins with structured loops (9-14 residues) buttressed by extensive hydrogen bonding interactions. Experimental characterization shows that the designs are monodisperse, highly soluble, folded and thermally stable. Crystal structures are in close agreement with the design models, with the loops structured and buttressed as designed. We demonstrate the functionality afforded by loop buttressing by designing and characterizing binders for extended peptides in which the loops form one side of an extended binding pocket. The ability to design multiple structured loops should contribute generally to efforts to design new protein functions. De novo design of buttressed loops for sculpting protein functions.,Jiang H, Jude KM, Wu K, Fallas J, Ueda G, Brunette TJ, Hicks DR, Pyles H, Yang A, Carter L, Lamb M, Li X, Levine PM, Stewart L, Garcia KC, Baker D Nat Chem Biol. 2024 Aug;20(8):974-980. doi: 10.1038/s41589-024-01632-2. Epub 2024 , May 30. PMID:38816644[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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