Competitive Microtubule Binding of PEX14 Coordinates Peroxisomal Protein Import and Motility. Issue 5 (5th March 2021)

• Record Type: Journal Article
• Authors: Reuter, Maren; Kooshapur, Hamed; Suda, Jeff-Gordian; Gaussmann, Stefan; Neuhaus, Alexander; Brühl, Lena; Bharti, Pratima; Jung, Martin; Schliebs, Wolfgang; Sattler, Michael; Erdmann, Ralf
• Is Part Of: Journal of molecular biology. Volume 433:Issue 5(2021)
• Publication Date: 2021-03-05
• Subjects: cytoskeleton -- peroxisome tethering -- PEX14 binding motifs -- PEX5 interaction -- kinesin motor domain; GST glutathione S-transferase -- MT microtubules -- NTD N-terminal domain -- PBD peroxisome biogenesis disorder -- PEX peroxins -- TEV tobacco etch virus protease cleavage site; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2020.166765
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: Human PEX14 facilitates peroxisomal protein import and microtubular attachment. Two PEX14- binding regions at the C-terminal region of ß-tubulin were identified. The protein import receptor PEX5 and MT compete for same binding site on PEX14. Competitive PEX14 interactions regulate peroxisome motility along microtubules. Abstract: Human PEX14 plays a dual role as docking protein in peroxisomal protein import and as peroxisomal anchor for microtubules (MT), which relates to peroxisome motility. For docking, the conserved N-terminal domain of PEX14 (PEX14-NTD) binds amphipathic alpha-helical ligands, typically comprising one or two aromatic residues, of which human PEX5 possesses eight. Here, we show that the PEX14-NTD also binds to microtubular filaments in vitro with a dissociation constant in nanomolar range. PEX14 interacts with two motifs in the C-terminal region of human ß-tubulin. At least one of the binding motifs is in spatial proximity to the binding site of microtubules (MT) for kinesin. Both PEX14 and kinesin can bind to MT simultaneously. Notably, binding of PEX14 to tubulin can be prevented by its association with PEX5. The data suggest that PEX5 competes peroxisome anchoring to MT by occupying the ß-tubulin-binding site of PEX14. The competitive correlation of matrix protein import and motility may facilitate the homogeneous dispersion of peroxisomes in mammalian cells.