PXD035668

PXD035668 is an original dataset announced via ProteomeXchange.

Title	Disordered region encodes α-crystallin chaperone activity toward lens client γD-crystallin
Description	Small heat-shock proteins (sHSPs) are a widely expressed family of ATP-independent molecular chaperones that are among the first responders to cellular stress. Mechanisms by which sHSPs delay aggregation of client proteins remain undefined. sHSPs have high intrinsic disorder content of up to ~60% and assemble into large, polydisperse homo- and hetero-oligomers, making them challenging structural and biochemical targets. Two sHSPs, HSPB4 and HSPB5, are present at millimolar concentrations in eye lens, where they are responsible for maintaining lens transparency over the lifetime of an organism. Together, HSPB4 and HSPB5 compose the hetero-oligomeric chaperone known as α-crystallin. To identify the determinants of sHSP function, we compared the effectiveness of HSPB4 and HSPB5 homo-oligomers and HSPB4/HSPB5 hetero-oligomers in delaying the aggregation of the lens protein γD-crystallin. In chimeric versions of HSPB4 and HSPB5, chaperone activity tracked with the identity of the 60-residue disordered N-terminal regions (NTR). A short 10-residue stretch in the middle of the NTR (“Critical sequence”) contains three residues that are responsible for high HSPB5 chaperone activity toward γD-crystallin. These residues affect structure and dynamics throughout the NTR. Abundant interactions involving the NTR Critical sequence reveal it to be a hub for a network of interactions within oligomers. We propose a model whereby the NTR critical sequence influences local structure and NTR dynamics that modulate accessibility of the NTR, which in turn modulates chaperone activity.
HostingRepository	PRIDE
AnnounceDate	2023-01-31
AnnouncementXML	Submission_2023-01-31_11:02:09.627.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lindsey D.Ulmer
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-01 02:40:37	ID requested
⏵ 1	2023-01-31 11:02:09	announced

Dataset with its publication pending

submitter keyword: HSPB5,Small Heat Shock Proteins, Crosslinking, BPA

Matthew F.Bush
contact affiliation	University of Washington Department of Chemistry
contact email	mattbush@uw.edu
lab head
Lindsey D.Ulmer
contact affiliation	University of Washington Department of Chemistry
contact email	lulmer@uw.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035668
     1. Label: PRIDE project
     2. Name: Disordered region encodes α-crystallin chaperone activity toward lens client γD-crystallin