TMEM106B in humans and Vac7 and Tag1 in yeast are predicted to be lipid transfer proteins.
Proteins
; 90(1): 164-175, 2022 01.
Article
in English
| MEDLINE | ID: covidwho-1340286
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
TMEM106B is an integral membrane protein of late endosomes and lysosomes involved in neuronal function, its overexpression 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-CoV-2 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 nonstandard way to show that the lumenal portion of TMEM106B is a member of the late embryogenesis abundant-2 (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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Carrier Proteins
/
Saccharomyces cerevisiae Proteins
/
Membrane Proteins
/
Nerve Tissue Proteins
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Proteins
Journal subject:
Biochemistry
Year:
2022
Document Type:
Article
Affiliation country:
Prot.26201
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