Competitive Microtubule Binding of PEX14 Coordinates Peroxisomal Protein Import and Motility |
| |
Affiliation: | 1. Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal;2. Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal;3. Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal |
| |
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. |
| |
Keywords: | cytoskeleton peroxisome tethering PEX14 binding motifs PEX5 interaction kinesin motor domain GST" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" glutathione S-transferase MT" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" microtubules NTD" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" N-terminal domain PBD" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" peroxisome biogenesis disorder PEX" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" peroxins TEV" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" tobacco etch virus protease cleavage site |
本文献已被 ScienceDirect 等数据库收录! |
|