title: Structure-function studies of an engineered scaffold protein derived from Stefin A. II: Development and applications of the SQT variant.
abstract: Constrained binding peptides (peptide aptamers) may serve as tools to explore protein conformations and disrupt protein-protein interactions. The quality of the protein scaffold, by which the binding peptide is constrained and presented, is of crucial importance. SQT (Stefin A Quadruple Mutant-Tracy) is our most recent development in the Stefin A-derived scaffold series. Stefin A naturally uses three surfaces to interact with its targets. SQT tolerates peptide insertions at all three positions. Peptide aptamers in the SQT scaffold can be expressed in bacterial, yeast and human cells, and displayed as a fusion to truncated pIII on phage. Peptides that bind to CDK2 can show improved binding in protein microarrays when presented by the SQT scaffold. Yeast two-hybrid libraries have been screened for binders to the POZ domain of BCL-6 and to a peptide derived from PBP2', specific to methicillin-resistant Staphylococcus aureus. Presentation of the Noxa BH3 helix by SQT allows specific interaction with Mcl-1 in human cells. Together, our results show that Stefin A-derived scaffolds, including SQT, can be used for a variety of applications in cellular and molecular biology. We will henceforth refer to Stefin A-derived engineered proteins as Scannins.
authors: Section of Experimental Therapeutics, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK.
authors: Lukas Kurt Josef
authors: LK
authors: Stadler
authors: Toni
authors: T
authors: Hoffmann
authors: Darren Charles
authors: DC
authors: Tomlinson
authors: Qifeng
authors: Q
authors: Song
authors: Tracy
authors: T
authors: Lee
authors: Michael
authors: M
authors: Busby
authors: Yvonne
authors: Y
authors: Nyathi
authors: Elisenda
authors: E
authors: Gendra
authors: Christian
authors: C
authors: Tiede
authors: Keith
authors: K
authors: Flanagan
authors: Simon J
authors: SJ
authors: Cockell
authors: Anil
authors: A
authors: Wipat
authors: Colin
authors: C
authors: Harwood
authors: Simon D
authors: SD
authors: Wagner
authors: Margaret A
authors: MA
authors: Knowles
authors: Jason J
authors: JJ
authors: Davis
authors: Neil
authors: N
authors: Keegan
authors: Paul Ko
authors: PK
authors: Ferrigno