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G Protein-Coupled Receptors Contain Two Conserved Packing Clusters

Sanchez-Reyes, OB and Cooke, ALG and Tranter, DB and Rashid, D and Eilers, M and Reeves, PJ and Smith, SO (2017) 'G Protein-Coupled Receptors Contain Two Conserved Packing Clusters.' Biophysical Journal, 112 (11). 2315 - 2326. ISSN 0006-3495

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Abstract

© 2017 Biophysical Society G protein-coupled receptors (GPCRs) have evolved a seven-transmembrane helix framework that is responsive to a wide range of extracellular signals. An analysis of the interior packing of family A GPCR crystal structures reveals two clusters of highly packed residues that facilitate tight transmembrane helix association. These clusters are centered on amino acid positions 2.47 and 4.53, which are highly conserved as alanine and serine, respectively. Ala2.47 mediates the interaction between helices H1 and H2, while Ser4.53 mediates the interaction between helices H3 and H4. The helical interfaces outside of these clusters are lined with residues that are more loosely packed, a structural feature that facilitates motion of helices H5, H6, and H7, which is required for receptor activation. Mutation of the conserved small side chain at position 4.53 within packing cluster 2 is shown to disrupt the structure of the visual receptor rhodopsin, whereas sites in packing cluster 1 (e.g., positions 1.46 and 2.47) are more tolerant to mutation but affect the overall stability of the protein. These findings reveal a common structural scaffold of GPCRs that is important for receptor folding and activation.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Depositing User: Philip Reeves
Date Deposited: 19 Jul 2017 11:24
Last Modified: 01 Aug 2019 13:18
URI: http://repository.essex.ac.uk/id/eprint/20097

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