Electrostatic and lipid anchor contributions to the interaction of transducin with membranes: Mechanistic implications for activation and translocation

Mickey Kosloff, Emil Alexov, Vadim Y. Arshavsky, Barry Honig

Research output: Contribution to journalArticlepeer-review


The heterotrimeric G protein transducin is a key component of the vertebrate phototransduction cascade. Transducin is peripherally attached to membranes of the rod outer segment, where it interacts with other proteins at the membrane-cytosol interface. However, upon sustained activation by light, the dissociated Gtα and Gβ1γ1 subunits of transducin translocate from the outer segment to other parts of the rod cell. Here we used a computational approach to analyze the interaction strength of transducin and its subunits with acidic lipid bilayers, as well as the range of orientations that they are allowed to occupy on the membrane surface. Our results suggest that the combined constraints of electrostatics and lipid anchors substantially limit the rotational degrees of freedom of the membrane-bound transducin heterotrimer. This may contribute to a faster transducin activation rate by accelerating transducin-rhodopsin complex formation. Notably, the membrane interactions of the dissociated transducin subunits are very different from those of the heterotrimer. As shown previously, Gβ1γ1 experiences significant attractive interactions with negatively charged membranes, whereas our new results suggest that Gtα is electrostatically repelled by such membranes. We suggest that this repulsion could facilitate the membrane dissociation and intracellular translocation of Gtα. Moreover, based on similarities in sequence and electrostatic properties, we propose that the properties described for transducin are common to its homologs within the G i subfamily. In a broader view, this work exemplifies how the activity-dependent association and dissociation of a G protein can change both the affinity for membranes and the range of allowed orientations, thereby modulating G protein function.

Original languageEnglish
Pages (from-to)31197-31207
Number of pages11
JournalJournal of Biological Chemistry
Issue number45
StatePublished - 7 Nov 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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