PXD062370-1

PXD062370 is an original dataset announced via ProteomeXchange.

Title	Distinct energetic blueprints diversify function of conserved protein folds
Description	While the ongoing revolution in structural biology offers an unprecedented understanding of the relationship between protein structure and function, it also confirms a puzzling, widely applicable principle: protein domains with highly conserved three-dimensional folds can perform radically disparate biochemical functions. To obtain insight to this fundamental structural enigma, we mapped the energetic landscapes of a family of bacterial transcription factors and their anciently diverged structural homologs, the periplasmic binding proteins. Using hydrogen exchange/mass spectrometry, bioinformatics, X-ray crystallography, and molecular dynamics, we uncovered an unexpected contrast: despite binding the same sugars, the two families evolved unique “energetic blueprints” to support their distinct functional requirements. To test if differences in ensemble energies have functional consequences, we rationally redesigned the protein fold for tunable ligand-driven transcriptional responses. Strikingly, energy-driven protein engineering produced synthetic transcription factors with the theoretically anticipated ligand-induced transcriptional outputs. Thus, decoding energetic blueprints among conserved protein folds provides a novel explanation for diverse functional adaptations, paves an alternative roadmap for protein design, and offers a new approach for engineering challenging drug targets.
HostingRepository	PRIDE
AnnounceDate	2026-05-26
AnnouncementXML	Submission_2026-05-26_01:30:27.511.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chenlin Lu
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: NEWT:562;
ModificationList	No PTMs are included in the dataset
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-29 01:14:09	ID requested
⏵ 1	2026-05-26 01:30:28	announced

Dataset with its publication pending

submitter keyword: None

Anum Glasgow
contact affiliation	Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY, United States
contact email	ag4522@cumc.columbia.edu
lab head
Chenlin Lu
contact affiliation	Columbia University Irving Medical Center
contact email	lucltsinghua@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062370
     1. Label: PRIDE project
     2. Name: Distinct energetic blueprints diversify function of conserved protein folds