Evidence map›Paper›PMID 33687327›Full record

ArticleeLife2021

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

Phil Huss, Anthony Meger, Megan Leander, Kyle Nishikawa, Srivatsan Raman

Abstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed.

  1. Review
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  10. ΦX174 bacteriophage viability predicted by protein biophysical modeling.bioRxiv : the preprint server for biology · 2025
    Article
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  20. Optimizing phage therapy with artificial intelligence: a perspective.Frontiers in cellular and infection microbiology · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Phil HussDepartment of Biochemistry, University of Wisconsin-Madison, Madison, United States.ORCID 0000-0003-4064-9333
Anthony MegerDepartment of Biochemistry, University of Wisconsin-Madison, Madison, United States.
Megan LeanderDepartment of Biochemistry, University of Wisconsin-Madison, Madison, United States.
Kyle NishikawaDepartment of Biochemistry, University of Wisconsin-Madison, Madison, United States.
Srivatsan RamanDepartment of Biochemistry, University of Wisconsin-Madison, Madison, United States.ORCID 0000-0003-2461-1589

Funding

GRADUATE TRAINING IN MOLECULAR BIOSCIENCEST32GM007215 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI HULL, CHRISTINA M · 1985 to 2018
$22.5M
PREDOCTORAL TRAINING IN MOLECULAR BIOPHYSICST32GM008293 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI JACKSON, MEYER B. · 1989 to 2016
$4.6M
Understanding molecular rules governing bacteriophage specificity and virulence by high-throughput mutational and metagenomic scanningR21AI156785 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI RAMAN, SRIVATSAN · 2021 to 2022
$427k
NIAID NIH HHS R21 AI156785NIGMS NIH HHS T32 GM007215NIGMS NIH HHS T32 GM008293NIH HHS T32 GM07215NIH HHS T32 GM08293
6 · The paper itself

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 variants against resistant hosts and host-constricting variants that eliminated certain hosts. To demonstrate therapeutic utility, we engineered highly active T7 variants against a urinary tract pathogen. Our approach presents a generalized framework for characterizing sequence-function relationships in many phage-bacterial systems.

Indexed as

MutationBacteriophage T7Genetic TechniquesProtein BindingViral ProteinsViral ProteinsBacteriophagebiochemistrychemical biologydeep mutational scanningphagesynthetic biologytail fibervirus

Identifiers

PMID33687327
PMCPMC8043750

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.