Linked Life Data

21182906

Source:http://linkedlifedata.com/resource/pubmed/id/21182906

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-3-22
pubmed:abstractText
Though the heterotrimeric G-proteins signaling system is one of the best studied in eukaryotes, its provenance and its prevalence outside of model eukaryotes remains poorly understood. We utilized the wealth of sequence data from recently sequenced eukaryotic genomes to uncover robust G-protein signaling systems in several poorly studied eukaryotic lineages such as the parabasalids, heteroloboseans and stramenopiles. This indicated that the G? subunit is likely to have separated from the ARF-like GTPases prior to the last eukaryotic common ancestor. We systematically identified the structure and sequence features associated with this divergence and found that most of the neomorphic positions in G? form a ring of residues centered on the nucleotide binding site, several of which are likely to be critical for interactions with the RGS domain for its GAP function. We also present evidence that in some of the potentially early branching eukaryotic lineages, like Trichomonas, G? is likely to function independently of the G?? subunits. We were able to identify previously unknown G? subunits in Naegleria, suggesting that the trimeric version was already present by the time of the divergence of the heteroloboseans from the remaining eukaryotes. Evolution of G? subunits is dominated by several independent lineage-specific expansions (LSEs). In most of these cases there are concomitant, independent LSEs of RGS proteins along with an extraordinary diversification of their domain architectures. The diversity of RGS domains from Naegleria in particular, which has the largest complement of G? and RGS proteins for any eukaryote, provides new insights into RGS function and evolution. We uncovered a new class of soluble ligand receptors of bacterial origin with RGS domains and an extraordinary diversity of membrane-linked, redox-associated, adhesion-dependent and small molecule-induced G-protein signaling networks that evolved in early-branching eukaryotes, independently of parallel systems in animals. Furthermore, this newly characterized diversity of RGS domains helps in defining their ancestral conserved interfaces with G? and also those interfaces that are prone to extensive lineage-specific diversification and are thereby responsible for selectivity in G?-RGS interactions. Several mushrooms show LSEs of G?s but not of RGS proteins pointing to the probable differentiation of G?s in conjunction with mating-type diversity. When combined with the characterization of the 7TM receptors (GPCRs), it becomes apparent that, through much of eukaryotic evolution, cells contained both 7TM receptors that acted as GEFs and those as GAPs (with C-terminal RGS domains) for G?s. Only in some lineages like animals and stramenopiles the 7TM receptors were restricted to GEF only roles, probably due to selection imposed by the rate-constants of the G?s that underwent lineage-specific expansion in them. In the alveolate lineage the 7TM receptors occur independently of heterotrimeric G-proteins, suggesting the prevalence of G-protein-independent signaling in these organisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1879-0038
pubmed:author
pubmed:copyrightInfo
Published by Elsevier B.V.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
475
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
63-78
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Comparative genomics uncovers novel structural and functional features of the heterotrimeric GTPase signaling system.
pubmed:affiliation
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Intramural