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An Indel in Transmembrane Helix 2 Helps to Trace the Molecular Evolution of Class A G-Protein-Coupled Receptors
被引:22
作者:
Deville, Julie
[1
]
Rey, Julien
[1
]
Chabbert, Marie
[1
]
机构:
[1] Fac Med, CNRS, UMR 6214, INSERM,U771, F-49045 Angers, France
关键词:
G-protein-coupled receptors;
Indel;
Structural evolution;
Proline;
Helical distortion;
CRYSTAL-STRUCTURE;
FUNCTIONAL-CHARACTERIZATION;
STRUCTURAL DIVERSITY;
SEQUENCE ALIGNMENT;
HUMAN GENOME;
RHODOPSIN;
ACTIVATION;
RESOLUTION;
INSERTIONS;
DELETIONS;
D O I:
10.1007/s00239-009-9214-9
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Class A G-protein-coupled receptors (GPCRs) constitute a large family of transmembrane receptors. Helical distortions play a major role in the overall fold of these receptors. Most are related to conserved proline residues. However, in transmembrane helix 2, the proline pattern is not conserved, and when present, proline may be located at position 2.58, 2.59, or 2.60. Sequence analysis, three-dimensional data mining, and molecular modeling were undertaken to investigate the origin of this unusual pattern. Taken together, the data strongly support the assumption that an indel led to two structural motifs for helix 2: a bulged structure in P2.59 and P2.60 receptors and a "typical" proline kink in P2.58 receptors. The proline pattern of helix 2 can be used as an evolutionary marker and helps to trace the molecular evolution of class A GPCRs. Two indel events yielding functional receptors occurred independently. One indel arose very early in GPCR evolution, in a bilaterian ancestor, before the protostome-deuterostome divergence. This indel led to the split between the P2.58 somatostatin/opioid receptors and other peptide receptors with the P2.59 pattern. A second indel also occurred in insect opsins and corresponds to a deletion. Subfamilies with proline at position 2.59 or no proline expanded earlier, whereas P2.60 receptors remained marginal throughout evolution. P2.58 receptors underwent rapid expansion in vertebrates with the development of the chemokine and purinergic receptor subfamilies from somatostatin/opioid-related ancestors.
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页码:475 / 489
页数:15
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