PXD038153

PXD038153 is an original dataset announced via ProteomeXchange.

Title	Hierarchical antagonistic regulatory elements in the TRPV4 intrinsically disordered N-terminus modulate lipid binding and channel activity through transient long-range interactions
Description	Intrinsically disordered regions (IDRs) are important for the functional regulation of membrane receptors. Among the TRP Vanilloid channels involved in thermo- and osmosensation, TRPV4 features the largest N-terminal IDR of ~150 residues. Here, we elucidate the structural ensemble of the TRPV4 IDR through an integrated structural biology approach. Novel structural and functional properties can be assigned to distinct IDR regions. Along the length of the entire IDR, a hierarchical interaction network of structurally and functionally coupled antagonistic regulatory modules can be mapped. Long-range transient crosstalk between these regulatory elements mediates channel responses to osmotic stimuli. Most notably, a highly conserved regulatory patch in the N-terminal IDR asserts dominant negative control over lipid binding and channel activity by acting on a sensitizing PIP2 binding site in the C-terminal IDR. This work demonstrates the importance of IDRs and “IDR cartography” for understanding TRP channel function and regulation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:04:25.831.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Florian Stengel
SpeciesList	scientific name: Gallus gallus (Chicken); NCBI TaxID: 9031;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-15 07:26:43	ID requested
1	2023-08-01 01:22:45	announced
⏵ 2	2023-11-14 09:04:30	announced	2023-11-14: Updated project metadata.

Goretzki B, Wiedemann C, McCray BA, Sch, ä, fer SL, Jansen J, Tebbe F, Mitrovic SA, N, ö, th J, Cabezudo AC, Donohue JK, Jeffries CM, Steinchen W, Stengel F, Sumner CJ, Hummer G, Hellmich UA, Crosstalk between regulatory elements in disordered TRPV4 N-terminus modulates lipid-dependent channel activity. Nat Commun, 14(1):4165(2023) [pubmed]

submitter keyword: TRP channel, integrated structural biology, intrinsically disordered protein, long-range communication, PIP2 binding

Florian Stengel
contact affiliation	Department of Biology, University of Konstanz, Universitätsstraße 10, 78457 Konstanz, Germany
contact email	florian.stengel@uni-konstanz.de
lab head
Florian Stengel
contact affiliation	Universität Konstanz
contact email	florian.stengel@uni-konstanz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038153
     1. Label: PRIDE project
     2. Name: Hierarchical antagonistic regulatory elements in the TRPV4 intrinsically disordered N-terminus modulate lipid binding and channel activity through transient long-range interactions