Levine, TP;
(2021)
TMEM106B in humans and Vac7 and Tag1 in yeast are predicted to be lipid transfer proteins.
Proteins: Structure, Function, and Bioinformatics
10.1002/prot.26201.
(In press).
Preview |
Text
Levine_TMEM106B in humans and Vac7 and Tag1 in yeast are predicted to be lipid transfer proteins_AOP.pdf - Published Version Download (4MB) | Preview |
Abstract
TMEM106B is an integral membrane protein of late endosomes and lysosomes involved in neuronal function, its over-expression being associated with familial frontotemporal lobar degeneration, and point mutation linked to hypomyelination. It has also been identified in multiple screens for host proteins required for productive SARS-CoV2 infection. Because standard approaches to understand TMEM106B at the sequence level find no homology to other proteins, it has remained a protein of unknown function. Here, the standard tool PSI-BLAST was used in a non-standard way to show that the lumenal portion of TMEM106B is a member of the LEA-2 domain superfamily. More sensitive tools (HMMER, HHpred and trRosetta) extended this to predict LEA-2 domains in two yeast proteins. One is Vac7, a regulator of PI(3,5)P2 production in the degradative vacuole, equivalent to the lysosome, which has a LEA-2 domain in its lumenal domain. The other is Tag1, another vacuolar protein, which signals to terminate autophagy and has three LEA-2 domains in its lumenal domain. Further analysis of LEA-2 structures indicated that LEA-2 domains have a long, conserved lipid binding groove. This implies that TMEM106B, Vac7 and Tag1 may all be lipid transfer proteins in the lumen of late endocytic organelles.
Type: | Article |
---|---|
Title: | TMEM106B in humans and Vac7 and Tag1 in yeast are predicted to be lipid transfer proteins |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1002/prot.26201 |
Publisher version: | https://doi.org/10.1002/prot.26201 |
Language: | English |
Additional information: | © 2021 The Author. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | endosome, LEA-2, lipid transfer protein, lysosome, structural bioinformatics, Tag1, TMEM106B, Vac7, vacuole, YLR173W |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
URI: | https://discovery.ucl.ac.uk/id/eprint/10132692 |
Archive Staff Only
![]() |
View Item |