PXD059353-1

PXD059353 is an original dataset announced via ProteomeXchange.

Title	Host-Switching Mutations in H5 Hemagglutinin Suppress Protein Dynamics at Activation pH
Description	Increase in the occurrence and severity of human H5N1 spillover infections resulting from dissemination of highly pathogenic avian influenza (HPAI) virus into bird and mammal populations raises concerns about HPAI adapting to become human transmissible. Studies identified hemagglutinin acid stability and receptor preference as essential molecular traits that shape host tropism. Mutations that increase hemagglutinin acid-stability and affinity for a-2,6-linked sialic acids have been shown to confer H5N1 airborne transmissibility in a ferret model. Here, we use hydrogen/deuterium-exchange mass spectrometry to dissect how airborne adaptation mutations impact dynamics during activation. Our results reveal that such mutations suppress dynamics in pH-responsive regions including the fusion peptide and receptor binding and fusion subunit interface, which would prevent premature inactivation during airborne transmission. These results for HPAI hemagglutinin identify regions that are hotspots for adaptive changes and reveal general influenza subtype-specific patterns.
HostingRepository	PRIDE
AnnounceDate	2025-10-30
AnnouncementXML	Submission_2025-10-29_20:04:33.948.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sally Kephart
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	SYNAPT G2-Si

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-01 13:09:47	ID requested
⏵ 1	2025-10-29 20:04:34	announced

10.1101/2025.10.06.680362;

ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)

submitter keyword: HDX-MS

Kelly K. Lee
contact affiliation	University of Washington Department of Medicinal Chemistry
contact email	kklee@uw.edu
lab head
Sally Kephart
contact affiliation	University of Washington
contact email	sallym8@uw.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/10/PXD059353

PRIDE project URI

• PRIDE
  1. PXD059353
     1. Label: PRIDE project
     2. Name: Host-Switching Mutations in H5 Hemagglutinin Suppress Protein Dynamics at Activation pH