2009 journal article
Membrane insertion of peptides mimicking E2 domain of Sindbis virus is modulated by cholesterol
Biophysical Journal, 96(3), 389a–390a.
TL;DR:
Investigation of the interaction of synthetic peptides mimicking E2 domain mutants with lipid bilayers with the goal to understand constraints placed upon membrane spanning domains for correct integration into the bilayer shows that cholesterol content of the lipid mixture modulates insertion of the peptides into bilayer mimicking mammalian cell membrane.
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UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: ORCID
Added: October 5, 2021
In the process of assembly Sindbis enveloped virus uses a host-derived membrane bilayer that is "sandwiched" between the concentric protein shells. The transmembrane domains of three glycoproteins penetrate the bilayer and are capable of assembling in two strikingly different membranes: mammalian membranes that contain up to 40% of cholesterol and insects membranes that contain larger fraction of shorter unsaturated lipids and no cholesterol. Recently, it was shown that mutations in the transmembrane domain of the Sindbis virus E2 protein produce deferential alterations in the protein association with the lipid bilayer: some mutants were able to grow in insect cells, but not in mammalian cells [1,2]. The Sindbis virus with STM-16 deletion mutation of the E2 transmembrane domain shows the most pronounced differential growth in mammal and insect cells while STM-18 shows almost wild-type behaviour. We have investigated the interaction of synthetic peptides mimicking E2 domain mutants with lipid bilayers with the goal to understand constraints placed upon membrane spanning domains for correct integration into the bilayer. The phospholipid composition was chosen to represent mammalian and insects' membranes. Results of EPR spin-labeling experiments show that both STM-16 and STM-18 peptides adopt a transmembrane configuration in bilayers with lipid composition mimicking that of insects. In mammalian cell mimicking membranes and containing cholesterol the STM-16 peptide aggregates at the surface of the bilayer. Both peptides exhibit transmembrane orientation in bilayers consisting of "mammalian" lipid mixture but without cholesterol. Thus, we show that cholesterol content of the lipid mixture modulates insertion of the peptides into bilayer mimicking mammalian cell membrane. Supported by NSF grant MCB-0451510 to TIS. [1] Hernandez, R., et. al. J Virol 2003 77(23), 12710-9. [2] West, J., et. al. J. Virol., 2006 80:4458-4468.