PXD041067

PXD041067 is an original dataset announced via ProteomeXchange.

Title	Structural dynamics of the chicken TRPV4 N-terminal domain
Description	Intrinsically disordered regions (IDRs) are essential for membrane receptor regulation but often remain unresolved in structural studies. TRPV4, a member of the TRP vanilloid channel family involved in thermo- and osmosensation, has a large N-terminal IDR of approximately 150 amino acids. With an integrated structural biology approach, we analyze the structural ensemble of the TRPV4 IDR and identify a network of regulatory elements that modulate channel activity in a hierarchical lipid-dependent manner through transient long-range interactions. A highly conserved autoinhibitory patch acts as a master regulator by competing with PIP2 binding to attenuate channel activity. Molecular dynamics simulations show that loss of the interaction between PIP2-binding site and the membrane reduces the force exerted by the IDR on the structured core of TRPV4. This work demonstrates that IDR structural dynamics are coupled to TRPV4 activity and highlights the importance of IDRs for TRP channel function and regulation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:10:32.564.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wieland Steinchen
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Gallus gallus (Chicken); NCBI TaxID: 9031;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-23 10:04:56	ID requested
1	2023-10-24 13:03:48	announced
⏵ 2	2023-11-14 09:10:40	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: TRPV4

Prof. Dr. Gert Bange
contact affiliation	Philipps-University Marburg, Center for Synthetic Microbiology (SYNMIKRO) & Faculty of Chemistry, Karl-von-Frisch-Straße 14, 35043 Marburg, Germany
contact email	gert.bange@synmikro.uni-marburg.de
lab head
Wieland Steinchen
contact affiliation	Philipps-University Marburg, Department of Chemistry & SYNMIKRO, Hans-Meerwein-Straße, 35043 Marburg, GERMANY
contact email	wieland.steinchen@synmikro.uni-marburg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041067
     1. Label: PRIDE project
     2. Name: Structural dynamics of the chicken TRPV4 N-terminal domain