The minor binding pocket: a major player in 7TM receptor activation

Novo Nordisk Foundation
Center for Basic Metabolic Research

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The minor binding pocket: a major player in 7TM receptor activation. / Rosenkilde, Mette Marie; Benned-Jensen, Tau; Frimurer, Thomas M.; Schwartz, Thue W.

In: Trends in Pharmacological Sciences, Vol. 31, No. 12, 2010, p. 567-574.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rosenkilde, MM, Benned-Jensen, T, Frimurer, TM & Schwartz, TW 2010, 'The minor binding pocket: a major player in 7TM receptor activation', Trends in Pharmacological Sciences, vol. 31, no. 12, pp. 567-574. https://doi.org/10.1016/j.tips.2010.08.006

APA

Rosenkilde, M. M., Benned-Jensen, T., Frimurer, T. M., & Schwartz, T. W. (2010). The minor binding pocket: a major player in 7TM receptor activation. Trends in Pharmacological Sciences, 31(12), 567-574. https://doi.org/10.1016/j.tips.2010.08.006

Vancouver

Rosenkilde MM, Benned-Jensen T, Frimurer TM, Schwartz TW. The minor binding pocket: a major player in 7TM receptor activation. Trends in Pharmacological Sciences. 2010;31(12):567-574. https://doi.org/10.1016/j.tips.2010.08.006

Author

Rosenkilde, Mette Marie ; Benned-Jensen, Tau ; Frimurer, Thomas M. ; Schwartz, Thue W. / The minor binding pocket: a major player in 7TM receptor activation. In: Trends in Pharmacological Sciences. 2010 ; Vol. 31, No. 12. pp. 567-574.

Bibtex

@article{722651cd1c5a48c4b956d63eb8baa57e,

title = "The minor binding pocket: a major player in 7TM receptor activation",

abstract = "From the deep part of the main ligand-binding crevice, a minor, often shallower pocket extends between the extracellular ends of transmembrane domains (TM)-I, II, III and VII of 7TM receptors. This minor binding pocket is defined by a highly conserved kink in TM-II that is induced by a proline residue located in one of two adjacent positions. Here we argue that this minor binding pocket is important for receptor activation. Functional coupling of the receptors seems to be mediated through the hydrogen bond network located between the intracellular segments of these TMs, with the allosteric interface between TM-II and TM-VII being of particular significance. Importantly, the minor binding pocket, especially the proline-kink in TM-II, is involved in G protein versus arrestin pathway-biased signaling, for example in the angiotensin AT1 system. Consequently, this pocket could be specifically targeted in the development of functionally biased drugs.",

keywords = "Animals, Binding Sites, Drug Delivery Systems, Humans, Ligands, Models, Molecular, Protein Structure, Quaternary, Receptors, G-Protein-Coupled, Signal Transduction",

author = "Rosenkilde, {Mette Marie} and Tau Benned-Jensen and Frimurer, {Thomas M.} and Schwartz, {Thue W.}",

year = "2010",

doi = "10.1016/j.tips.2010.08.006",

language = "English",

volume = "31",

pages = "567--574",

journal = "Trends in Pharmacological Sciences",

issn = "0165-6147",

publisher = "Elsevier Ltd. * Trends Journals",

number = "12",

}

RIS

TY - JOUR

T1 - The minor binding pocket: a major player in 7TM receptor activation

AU - Rosenkilde, Mette Marie

AU - Benned-Jensen, Tau

AU - Frimurer, Thomas M.

AU - Schwartz, Thue W.

PY - 2010

Y1 - 2010

N2 - From the deep part of the main ligand-binding crevice, a minor, often shallower pocket extends between the extracellular ends of transmembrane domains (TM)-I, II, III and VII of 7TM receptors. This minor binding pocket is defined by a highly conserved kink in TM-II that is induced by a proline residue located in one of two adjacent positions. Here we argue that this minor binding pocket is important for receptor activation. Functional coupling of the receptors seems to be mediated through the hydrogen bond network located between the intracellular segments of these TMs, with the allosteric interface between TM-II and TM-VII being of particular significance. Importantly, the minor binding pocket, especially the proline-kink in TM-II, is involved in G protein versus arrestin pathway-biased signaling, for example in the angiotensin AT1 system. Consequently, this pocket could be specifically targeted in the development of functionally biased drugs.

AB - From the deep part of the main ligand-binding crevice, a minor, often shallower pocket extends between the extracellular ends of transmembrane domains (TM)-I, II, III and VII of 7TM receptors. This minor binding pocket is defined by a highly conserved kink in TM-II that is induced by a proline residue located in one of two adjacent positions. Here we argue that this minor binding pocket is important for receptor activation. Functional coupling of the receptors seems to be mediated through the hydrogen bond network located between the intracellular segments of these TMs, with the allosteric interface between TM-II and TM-VII being of particular significance. Importantly, the minor binding pocket, especially the proline-kink in TM-II, is involved in G protein versus arrestin pathway-biased signaling, for example in the angiotensin AT1 system. Consequently, this pocket could be specifically targeted in the development of functionally biased drugs.

KW - Animals

KW - Binding Sites

KW - Drug Delivery Systems

KW - Humans

KW - Ligands

KW - Models, Molecular

KW - Protein Structure, Quaternary

KW - Receptors, G-Protein-Coupled

KW - Signal Transduction

U2 - 10.1016/j.tips.2010.08.006

DO - 10.1016/j.tips.2010.08.006

M3 - Journal article

C2 - 20870300

VL - 31

SP - 567

EP - 574

JO - Trends in Pharmacological Sciences

JF - Trends in Pharmacological Sciences

SN - 0165-6147

IS - 12

ER -

ID: 34356196

Novo Nordisk Foundation Center for Basic Metabolic Research