Defining short linear motif binding determinants by phage display-based deep mutational scanning.

ABSTRACT: Deep mutational scanning (DMS) has emerged as a powerful approach for evaluating the effects of mutations on binding or function. Here, we developed a DMS by phage display protocol to define the specificity determinants of short linear motifs (SLiMs) binding to peptide-binding domains. We first designed a benchmarking DMS library to evaluate the performance of the approach on well-known ligands for 11 different peptide-binding domains, including the talin-1 PTB domain, the G3BP1 NTF2 domain, and the MDM2 SWIB domain. Comparison with a set of reference motifs from the eukaryotic linear motif (ELM) database confirmed that the DMS by phage display analysis correctly identifies known motif binding determinants and provides novel insights into specificity determinants, including defining a non-

SUBMITTER: Benz C 

PROVIDER: S-EPMC12102759 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature