Evolutionary remodeling of a remnant GET pathway factor into PEX38, an essential peroxin.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41746722.
- Also identified by DOI 10.1073/pnas.2533726123 and PMC identifier 12956874.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
PEX19 is a cytosolic receptor that directs membrane proteins posttranslationally to peroxisomes, as well as to mitochondria, lipid droplets, and the endoplasmic reticulum. A comprehensive <i>Trypanosoma</i> PEX19 interactome analysis uncovered PEX38 as an essential Euglenozoa-specific peroxin. PEX38 contains distinct domains that bind the cochaperone Hip and the PEX3-binding motif of PEX19, suggesting a role in stabilizing membrane proteins and preventing premature membrane docking. PEX38 illustrates functional repurposing in organelle biogenesis. It originated from a remnant of the GET/TRC pathway, typically responsible for the targeting of tail-anchored (TA) proteins to the endoplasmic reticulum. While most components of this machinery are absent in Euglenozoa, PEX38 has been retained and adapted to mediate peroxisomal membrane protein targeting. This evolutionary adaptation is unique to Euglenozoa. Because the PEX19-PEX38 interaction is essential for parasite viability and PEX38 has no human homologs, this complex is a promising therapeutic target against trypanosomatid parasites.