Name: Structural dynamics of the chicken TRPV4 N-terminal domain
Keywords: Trpv4

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Structural dynamics of the chicken TRPV4 N-terminal domain

ABSTRACT: 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.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Gallus Gallus (chicken) Escherichia Coli

SUBMITTER: Wieland Steinchen

LAB HEAD: Prof. Dr. Gert Bange

PROVIDER: PXD041067 | Pride | 2023-10-24

REPOSITORIES: Pride

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			Action	DRS
	220222_HX_412_Ba_A.DnX	Other
	220222_HX_412_Ba_ARD1.zip	Other
	220222_HX_412_Ba_ARD2.zip	Other
	220222_HX_412_Ba_ARD3.zip	Other
	220222_HX_412_Ba_B.DnX	Other

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