The Library
One motif to bind them : a small-XXX-small motif affects transmembrane domain 1 oligomerization, function, localization, and cross-talk between two yeast GPCRs
Tools
Tools
Tools
Lock, Antonia, Forfar, Rachel, Weston, Cathryn, Bowsher, L, Upton, Graham J.G., Reynolds, Christopher A., Ladds, Graham and Dixon, Ann M. (2014) One motif to bind them : a small-XXX-small motif affects transmembrane domain 1 oligomerization, function, localization, and cross-talk between two yeast GPCRs. Biochimica et Biophysica Acta (BBA) - Biomembranes, Volume 1838 (Number 12). pp. 3036-3051. doi:10.1016/j.bbamem.2014.08.019
Research output not available from this repository.
Request-a-Copy directly from author or use local Library Get it For Me service.
Official URL: http://dx.doi.org/10.1016/j.bbamem.2014.08.019
Abstract
G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors in mammals and facilitate a range of physiological responses triggered by a variety of ligands. GPCRs were thought to function as monomers, however it is now accepted that GPCR homo- and hetero-oligomers also exist and influence receptor properties. The Schizosaccharomyces pombe GPCR Mam2 is a pheromone-sensing receptor involved in mating and has previously been shown to form oligomers in vivo. The first transmembrane domain (TMD) of Mam2 contains a small-XXX-small motif, overrepresented in membrane proteins and well-known for promoting helix-helix interactions. An ortholog of Mam2 in Saccharomyces cerevisiae, Ste2, contains an analogous small-XXX-small motif which has been shown to contribute to receptor homo-oligomerization, localization and function. Here we have used experimental and computational techniques to characterize the role of the small-XXX-small motif in function and assembly of Mam2 for the first time. We find that disruption of the motif via mutagenesis leads to reduction of Mam2 TMD1 homo-oligomerization and pheromone-responsive cellular signaling of the full-length protein. It also impairs correct targeting to the plasma membrane. Mutation of the analogous motif in Ste2 yielded similar results, suggesting a conserved mechanism for assembly. Using co-expression of the two fungal receptors in conjunction with computational models, we demonstrate a functional change in G protein specificity and propose that this is brought about through hetero-dimeric interactions of Mam2 with Ste2 via the complementary small-XXX-small motifs. This highlights the potential of these motifs to affect a range of properties that can be investigated in other GPCRs.
| Item Type: | Journal Article | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
||||||||||
| Journal or Publication Title: | Biochimica et Biophysica Acta (BBA) - Biomembranes | ||||||||||
| Publisher: | Elsevier BV | ||||||||||
| ISSN: | 0005-2736 | ||||||||||
| Official Date: | December 2014 | ||||||||||
| Dates: |
|
||||||||||
| Volume: | Volume 1838 | ||||||||||
| Number: | Number 12 | ||||||||||
| Page Range: | pp. 3036-3051 | ||||||||||
| DOI: | 10.1016/j.bbamem.2014.08.019 | ||||||||||
| Status: | Peer Reviewed | ||||||||||
| Publication Status: | Published | ||||||||||
| Access rights to Published version: | Restricted or Subscription Access |
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
