NDLI: A general model of G protein-coupled receptor sequences and its application to detect remote homologs

Content Provider	PubMed Central
Author	Markus, Wistrand Lukas, Käll Sonnhammer, Erik L. L.
Abstract	G protein-coupled receptors (GPCRs) constitute a large superfamily involved in various types of signal transduction pathways triggered by hormones, odorants, peptides, proteins, and other types of ligands. The superfamily is so diverse that many members lack sequence similarity, although they all span the cell membrane seven times with an extracellular N and a cytosolic C terminus. We analyzed a divergent set of GPCRs and found distinct loop length patterns and differences in amino acid composition between cytosolic loops, extracellular loops, and membrane regions. We configured GPCRHMM, a hidden Markov model, to fit those features and trained it on a large dataset representing the entire superfamily. GPCRHMM was benchmarked to profile HMMs and generic transmembrane detectors on sets of known GPCRs and non-GPCRs. In a cross-validation procedure, profile HMMs produced an error rate nearly twice as high as GPCRHMM. In a sensitivity-selectivity test, GPCRHMM’s sensitivity was about 15% higher than that of the best transmembrane predictors, at comparable false positive rates. We used GPCRHMM to search for novel members of the GPCR superfamily in five proteomes. All in all we detected 120 sequences that lacked annotation and are potentially novel GPCRs. Out of those 102 were found in Caenorhabditis elegans, four in human, and seven in mouse. Many predictions (65) belonged to Pfam domains of unknown function. GPCRHMM strongly rejected a family of arthropod-specific odorant receptors believed to be GPCRs. A detailed analysis showed that these sequences are indeed very different from other GPCRs. GPCRHMM is available at http://gpcrhmm.cgb.ki.se.
Related Links	http://dx.doi.org/10.1110/ps.051745906
Starting Page	509
File Format	PDF
ISSN	1469896X
e-ISSN	1469896X
Journal	Protein Science : A Publication of the Protein Society
Issue Number	3
Volume Number	15
Language	English
Publisher	Cold Spring Harbor Laboratory Press
Publisher Date	2006-03-01
Access Restriction	Open
Rights Holder	Cold Spring Harbor Laboratory Press
Subject Keyword	Proteomics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine Molecular Biology Biochemistry

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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