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  Cryo-EM structure of the active, G(s)- protein complexed, human CGRP receptor

Liang, Y.-L., Khoshouei, M., Deganutti, G., Glukhova, A., Koole, C., Peat, T. S., et al. (2018). Cryo-EM structure of the active, G(s)- protein complexed, human CGRP receptor. Nature, 561(7724), 492-497. doi:10.1038/s41586-018-0535-y.

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 Creators:
Liang, Yi-Lynn1, Author
Khoshouei, Maryam2, Author              
Deganutti, Giuseppe1, Author
Glukhova, Alisa1, Author
Koole, Cassandra1, Author
Peat, Thomas S.1, Author
Radjainia, Mazdak1, Author
Plitzko, Jürgen M.2, Author              
Baumeister, Wolfgang2, Author              
Miller, Laurence J.1, Author
Hay, Deborah L.1, Author
Christopoulos, Arthur1, Author
Reynolds, Christopher A.1, Author
Wootten, Denise1, Author
Sexton, Patrick M.1, Author
Affiliations:
1external, ou_persistent22              
2Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565142              

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Free keywords: GENE-RELATED PEPTIDE; ACTIVITY-MODIFYING PROTEINS; CLASS-B GPCR; MOLECULAR-DYNAMICS; COUPLED RECEPTOR; GLP-1 RECEPTOR; PHASE-PLATE; EXTRACELLULAR LOOPS; RAMPS; FAMILYScience & Technology - Other Topics;
 Abstract: Calcitonin gene-related peptide (CGRP) is a widely expressed neuropeptide that has a major role in sensory neurotransmission. The CGRP receptor is a heterodimer of the calcitonin receptor-like receptor (CLR) class B G-protein-coupled receptor and a type 1 transmembrane domain protein, receptor activity-modifying protein 1 (RAMP1). Here we report the structure of the human CGRP receptor in complex with CGRP and the G(s)-protein heterotrimer at 3.3 A global resolution, determined by Volta phase-plate cryo-electron microscopy. The receptor activity-modifying protein transmembrane domain sits at the interface between transmembrane domains 3, 4 and 5 of CLR, and stabilizes CLR extracellular loop 2. RAMP1 makes only limited direct contact with CGRP, consistent with its function in allosteric modulation of CLR. Molecular dynamics simulations indicate that RAMP1 provides stability to the receptor complex, particularly in the positioning of the extracellular domain of CLR. This work provides insights into the control of G-protein-coupled receptor function.

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Language(s): eng - English
 Dates: 2018
 Publication Status: Published in print
 Pages: 21
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000445622500047
DOI: 10.1038/s41586-018-0535-y
 Degree: -

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Title: Nature
  Abbreviation : Nature
Source Genre: Journal
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Affiliations:
Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 561 (7724) Sequence Number: - Start / End Page: 492 - 497 Identifier: ISSN: 0028-0836
CoNE: https://pure.mpg.de/cone/journals/resource/954925427238