Journal
BIOMEDICINES
Volume 11, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/biomedicines11020557
Keywords
drug discovery; lipid rafts; membrane lipids; palmitoylation; protein structure; protein prenylation; lipid structure; protein-lipid interactions; membrane microdomain; cell signaling; membrane lipid therapy; melitherapy
Ask authors/readers for more resources
GPCR interacts with lipids to bring G proteins together in specific membrane microdomains, enabling efficient signal transduction. The lipid composition and specific protein regions play a crucial role, but the molecular mechanisms underlying the membrane distribution of each G protein isoform are still largely unknown.
GPCRs receive signals from diverse messengers and activate G proteins that regulate downstream signaling effectors. Efficient signaling is achieved through the organization of these proteins in membranes. Thus, protein-lipid interactions play a critical role in bringing G proteins together in specific membrane microdomains with signaling partners. Significantly, the molecular basis underlying the membrane distribution of each G protein isoform, fundamental to fully understanding subsequent cell signaling, remains largely unclear. We used model membranes with lipid composition resembling different membrane microdomains, and monomeric, dimeric and trimeric Gi proteins with or without single and multiple mutations to investigate the structural bases of G protein-membrane interactions. We demonstrated that cationic amino acids in the N-terminal region of the G alpha i(1) and C-terminal region of the G gamma(2) subunit, as well as their myristoyl, palmitoyl and geranylgeranyl moieties, define the differential G protein form interactions with membranes containing different lipid classes (PC, PS, PE, SM, Cho) and the various microdomains they may form (Lo, Ld, PC bilayer, charged, etc.). These new findings in part explain the molecular basis underlying amphitropic protein translocation to membranes and localization to different membrane microdomains and the role of these interactions in cell signal propagation, pathophysiology and therapies targeted to lipid membranes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available