NDLI: Conformational dynamics of helix 8 in the GPCR rhodopsin controls arrestin activation in the desensitization process

Content Provider	PubMed Central
Author	Kirchberg, Kristina Kim, Tai-yang Möller, Martina Darko, Skegro Raju, Gayathri Dasara Granzin, Joachim Georg, Büldt Schlesinger, Ramona Alexiev, Ulrike
Abstract	Arrestins are regulatory molecules for G-protein coupled receptor function. In visual rhodopsin, selective binding of arrestin to the cytoplasmic side of light-activated, phosphorylated rhodopsin (P-Rh) terminates signaling via the G-protein transducin. While the “phosphate-sensor” of arrestin for the recognition of receptor-attached phosphates is identified, the molecular mechanism of arrestin binding and the involvement of receptor conformations in this process are still largely hypothetic. Here we used fluorescence pump-probe and time-resolved fluorescence depolarization measurements to investigate the kinetics of arrestin conformational changes and the corresponding nanosecond dynamical changes at the receptor surface. We show that at least two sequential conformational changes of arrestin occur upon interaction with P-Rh, thus providing a kinetic proof for the suggested multistep nature of arrestin binding. At the cytoplasmic surface of P-Rh, the structural dynamics of the amphipathic helix 8 (H8), connecting transmembrane helix 7 and the phosphorylated C-terminal tail, depends on the arrestin interaction state. We find that a high mobility of H8 is required in the low-affinity (prebinding) but not in the high-affinity binding state. High-affinity arrestin binding is inhibited when a bulky, inflexible group is bound to H8, indicating close interaction. We further show that this close steric interaction of H8 with arrestin is mandatory for the transition from prebinding to high-affinity binding; i.e., for arrestin activation. This finding implies a regulatory role for H8 in activation of visual arrestin, which shows high selectivity to P-Rh in contrast to the broad receptor specificity displayed by the two nonvisual arrestins.
Related Links	http://dx.doi.org/10.1073/pnas.1015461108
Ending Page	18695
Page Count	6
Starting Page	18690
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	46
Volume Number	108
Language	English
Publisher	National Academy of Sciences
Publisher Date	2011-11-15
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Conformational dynamics of helix 8 in the GPCR rhodopsin controls arrestin activation in the desensitization process.

Experimental and Computational Studies of the Desensitization Process in the Bovine Rhodopsin-Arrestin Complex

Structural waters define a functional channel mediating activation of the GPCR, rhodopsin

Monomeric Rhodopsin Is Sufficient for Normal Rhodopsin Kinase (GRK1) Phosphorylation and Arrestin-1 Binding

GPCR-biased control of the endocytic network by β-arrestin

Distinct conformations of GPCR–β-arrestin complexes mediate desensitization, signaling, and endocytosis

Conformational Selection and Equilibrium Governs the Ability of Retinals to Bind Opsin

Each rhodopsin molecule binds its own arrestin

Targeting of Drosophila Rhodopsin Requires Helix 8 but Not the Distal C-Terminus

Conformational dynamics of helix 8 in the GPCR rhodopsin controls arrestin activation in the desensitization process

Similar Documents

Conformational dynamics of helix 8 in the GPCR rhodopsin controls arrestin activation in the desensitization process.

Experimental and Computational Studies of the Desensitization Process in the Bovine Rhodopsin-Arrestin Complex

Structural waters define a functional channel mediating activation of the GPCR, rhodopsin

Monomeric Rhodopsin Is Sufficient for Normal Rhodopsin Kinase (GRK1) Phosphorylation and Arrestin-1 Binding

GPCR-biased control of the endocytic network by β-arrestin

Distinct conformations of GPCR–β-arrestin complexes mediate desensitization, signaling, and endocytosis

Conformational Selection and Equilibrium Governs the Ability of Retinals to Bind Opsin

Each rhodopsin molecule binds its own arrestin

Targeting of Drosophila Rhodopsin Requires Helix 8 but Not the Distal C-Terminus

Conformational dynamics of helix 8 in the GPCR rhodopsin controls arrestin activation in the desensitization process