Common evolutionary binding mode of rhodopsin-like GPCRs: Insights from structural bioinformatics

Eda Suku; Alejandro Giorgetti; Eda Suku; Alejandro Giorgetti

doi:10.3934/biophy.2017.4.543

AIMS Biophysics

2017, Volume 4, Issue 4: 543-556. doi: 10.3934/biophy.2017.4.543

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Research article

Common evolutionary binding mode of rhodopsin-like GPCRs: Insights from structural bioinformatics

Eda Suku ¹,
Alejandro Giorgetti ^{1,2
,
,}

1.
Department of Biotechnology, University of Verona, Ca’ Vignal 1, Strada le Grazie 15, 37134 Verona, Italy
2.
Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, 52425 Jülich, Germany

Received: 04 August 2017 Accepted: 17 September 2017 Published: 26 September 2017

G-protein Coupled Receptors (GPCRs) form the largest membrane protein superfamily in vertebrates. Advances in crystallization techniques so far resulted in the resolution of 44 unique receptors available for the GPCRs researcher’s community, 37 of which belong to rhodopsin-like GPCRs class. We performed here the first systematic analysis of GPCRs binding cavities based on the available pool of rhodopsin-like solved structures. We pinpointed ten positions shared between all the solved receptors, namely 3.32, 3.33, 3,36, 6.48, 6.51, 6.52, 6.55, 7.35, 7.39 and 7.43, as interacting with ligands. We analyzed the conservation of amino acids present in these positions and clustered GPCRs accordingly to the physicochemical properties of binding cavities’ residues. Clustering supplied new interesting insights into the common binding mode of these receptors. In particular, the 3.32 position turned out to have an important role in ligand charge detection. Finally, we demonstrated that residues in these ten positions have co-evolved together, sharing a common evolutionary history.
- GPCRs,
- bioinformatics,
- structural analysis,
- clustering,
- GPCRs evolution
Citation: Eda Suku, Alejandro Giorgetti. Common evolutionary binding mode of rhodopsin-like GPCRs: Insights from structural bioinformatics[J]. AIMS Biophysics, 2017, 4(4): 543-556. doi: 10.3934/biophy.2017.4.543

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Abstract

G-protein Coupled Receptors (GPCRs) form the largest membrane protein superfamily in vertebrates. Advances in crystallization techniques so far resulted in the resolution of 44 unique receptors available for the GPCRs researcher’s community, 37 of which belong to rhodopsin-like GPCRs class. We performed here the first systematic analysis of GPCRs binding cavities based on the available pool of rhodopsin-like solved structures. We pinpointed ten positions shared between all the solved receptors, namely 3.32, 3.33, 3,36, 6.48, 6.51, 6.52, 6.55, 7.35, 7.39 and 7.43, as interacting with ligands. We analyzed the conservation of amino acids present in these positions and clustered GPCRs accordingly to the physicochemical properties of binding cavities’ residues. Clustering supplied new interesting insights into the common binding mode of these receptors. In particular, the 3.32 position turned out to have an important role in ligand charge detection. Finally, we demonstrated that residues in these ten positions have co-evolved together, sharing a common evolutionary history.

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