Abstract
Ice2p is an integral endoplasmic reticulum (ER) membrane protein in budding yeast S. cerevisiae named ICE because it is required for Inheritance of Cortical ER. Ice2p has also been reported to be involved in an ER metabolic branch-point that regulates the flux of lipid either to be stored in lipid droplets or to be used as membrane components. Alternately, Ice2p has been proposed to act as a tether that physically bridges the ER at contact sites with both lipid droplets and the plasma membrane via a long loop on the protein’s cytoplasmic face that contains multiple predicted amphipathic helices. Here we carried out a bioinformatic analysis to increase understanding of Ice2p. Firstly, regarding topology, we found that diverse members of the fungal Ice2 family have ten transmembrane helices, which places the long loop on the exofacial face of Ice2p, where it cannot form inter-organelle bridges. Secondly, we identified Ice2 as a full-length homologue of SERINC (serine incorporator), a family of proteins with ten transmembrane helices found universally in eukaryotes. Since SERINCs are potent restriction factors for HIV and other viruses, study of Ice2p may reveal functions or mechanisms that shed light on viral restriction by SERINCs.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Conflict of interest disclosure: the authors declare that there are no conflicts of interest.
Data availability statement: Data that support this study are freely available in Harvard Dataverse at https://dataverse.harvard.edu/dataverse/Ice2_SERINC.
The strength of the homology between Ice2 and SERINC has been stressed by 1) clarifying that the link can be made by PSI-BLAST alone 2) showing the highly significant E-value (4e-9) obtained for sequence alignment alone in HHpred 3) using HMM profile-sequence tools (iterative HMMER and HHblits) to make the link, and explaining that yeast-only loops in Ice2 obstruct the tools. 4) verifying the result with other template based tools: FFAS03, Phyre2, Galaxy, Swiss-Model; and also providing evidence from contact-folding based tools: trRosetta and RaptorX. Some of the conclusions and discussion has been nuannced to tone down some over-simplifications in the first draft.
