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Molecular basis of the glycosomal targeting of PEX11 and its mislocalization to mitochondrion in trypanosomes

PEX19 binding sites are essential parts of the targeting signals of peroxisomal membrane proteins (mPTS). In this study, we characterized PEX19 binding sites of PEX11, the most abundant peroxisomal and glycosomal membrane protein from Trypanosoma brucei and Saccharomyces cerevisiae. TbPEX11 contains...

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Autores principales: Krishna, Chethan K., Schmidt, Nadine, Tippler, Bettina G., Schliebs, Wolfgang, Jung, Martin, Winklhofer, Konstanze F., Erdmann, Ralf, Kalel, Vishal C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10469627/
https://www.ncbi.nlm.nih.gov/pubmed/37664461
http://dx.doi.org/10.3389/fcell.2023.1213761
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author Krishna, Chethan K.
Schmidt, Nadine
Tippler, Bettina G.
Schliebs, Wolfgang
Jung, Martin
Winklhofer, Konstanze F.
Erdmann, Ralf
Kalel, Vishal C.
author_facet Krishna, Chethan K.
Schmidt, Nadine
Tippler, Bettina G.
Schliebs, Wolfgang
Jung, Martin
Winklhofer, Konstanze F.
Erdmann, Ralf
Kalel, Vishal C.
author_sort Krishna, Chethan K.
collection PubMed
description PEX19 binding sites are essential parts of the targeting signals of peroxisomal membrane proteins (mPTS). In this study, we characterized PEX19 binding sites of PEX11, the most abundant peroxisomal and glycosomal membrane protein from Trypanosoma brucei and Saccharomyces cerevisiae. TbPEX11 contains two PEX19 binding sites, one close to the N-terminus (BS1) and a second in proximity to the first transmembrane domain (BS2). The N-terminal BS1 is highly conserved across different organisms and is required for maintenance of the steady-state concentration and efficient targeting to peroxisomes and glycosomes in both baker’s yeast and Trypanosoma brucei. The second PEX19 binding site in TbPEX11 is essential for its glycosomal localization. Deletion or mutations of the PEX19 binding sites in TbPEX11 or ScPEX11 results in mislocalization of the proteins to mitochondria. Bioinformatic analysis indicates that the N-terminal region of TbPEX11 contains an amphiphilic helix and several putative TOM20 recognition motifs. We show that the extreme N-terminal region of TbPEX11 contains a cryptic N-terminal signal that directs PEX11 to the mitochondrion if its glycosomal transport is blocked.
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spelling pubmed-104696272023-09-01 Molecular basis of the glycosomal targeting of PEX11 and its mislocalization to mitochondrion in trypanosomes Krishna, Chethan K. Schmidt, Nadine Tippler, Bettina G. Schliebs, Wolfgang Jung, Martin Winklhofer, Konstanze F. Erdmann, Ralf Kalel, Vishal C. Front Cell Dev Biol Cell and Developmental Biology PEX19 binding sites are essential parts of the targeting signals of peroxisomal membrane proteins (mPTS). In this study, we characterized PEX19 binding sites of PEX11, the most abundant peroxisomal and glycosomal membrane protein from Trypanosoma brucei and Saccharomyces cerevisiae. TbPEX11 contains two PEX19 binding sites, one close to the N-terminus (BS1) and a second in proximity to the first transmembrane domain (BS2). The N-terminal BS1 is highly conserved across different organisms and is required for maintenance of the steady-state concentration and efficient targeting to peroxisomes and glycosomes in both baker’s yeast and Trypanosoma brucei. The second PEX19 binding site in TbPEX11 is essential for its glycosomal localization. Deletion or mutations of the PEX19 binding sites in TbPEX11 or ScPEX11 results in mislocalization of the proteins to mitochondria. Bioinformatic analysis indicates that the N-terminal region of TbPEX11 contains an amphiphilic helix and several putative TOM20 recognition motifs. We show that the extreme N-terminal region of TbPEX11 contains a cryptic N-terminal signal that directs PEX11 to the mitochondrion if its glycosomal transport is blocked. Frontiers Media S.A. 2023-08-17 /pmc/articles/PMC10469627/ /pubmed/37664461 http://dx.doi.org/10.3389/fcell.2023.1213761 Text en Copyright © 2023 Krishna, Schmidt, Tippler, Schliebs, Jung, Winklhofer, Erdmann and Kalel. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Krishna, Chethan K.
Schmidt, Nadine
Tippler, Bettina G.
Schliebs, Wolfgang
Jung, Martin
Winklhofer, Konstanze F.
Erdmann, Ralf
Kalel, Vishal C.
Molecular basis of the glycosomal targeting of PEX11 and its mislocalization to mitochondrion in trypanosomes
title Molecular basis of the glycosomal targeting of PEX11 and its mislocalization to mitochondrion in trypanosomes
title_full Molecular basis of the glycosomal targeting of PEX11 and its mislocalization to mitochondrion in trypanosomes
title_fullStr Molecular basis of the glycosomal targeting of PEX11 and its mislocalization to mitochondrion in trypanosomes
title_full_unstemmed Molecular basis of the glycosomal targeting of PEX11 and its mislocalization to mitochondrion in trypanosomes
title_short Molecular basis of the glycosomal targeting of PEX11 and its mislocalization to mitochondrion in trypanosomes
title_sort molecular basis of the glycosomal targeting of pex11 and its mislocalization to mitochondrion in trypanosomes
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10469627/
https://www.ncbi.nlm.nih.gov/pubmed/37664461
http://dx.doi.org/10.3389/fcell.2023.1213761
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