Mapping the functional landscape of the receptor binding domain of T7 bacteriophage by deep mutational scanning.

ABSTRACT: The interaction between a bacteriophage and its host is mediated by the phage's receptor binding protein (RBP). Despite its fundamental role in governing phage activity and host range, molecular rules of RBP function remain a mystery. Here, we systematically dissect the functional role of every residue in the tip domain of T7 phage RBP (1660 variants) by developing a high-throughput, locus-specific, phage engineering method. This rich dataset allowed us to cross compare functional profiles across hosts to precisely identify regions of functional importance, many of which were previously unknown. Substitution patterns showed host-specific differences in position and physicochemical properties of mutations, revealing molecular adaptation to individual hosts. We discovered gain-of-function va

SUBMITTER: Huss P 

PROVIDER: S-EPMC8043750 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature