Allosteric modulation of peroxisomal membrane protein
recognition by farnesylation of the peroxisomal import receptor
PEX19

J 2017

Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19

EMMANOUILIDIS, L., U. SCHUTZ, Konstantinos TRIPSIANES, T. MADL, J. RADKE et. al.

Základní údaje

Originální název

Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19

Autoři

EMMANOUILIDIS, L. (276 Německo), U. SCHUTZ (276 Německo), Konstantinos TRIPSIANES (300 Řecko, garant, domácí), T. MADL (40 Rakousko), J. RADKE (276 Německo), R. RUCKTASCHEL (276 Německo), M. WILMANNS (276 Německo), W. SCHLIEBS (276 Německo), R. ERDMANN (276 Německo) a M. SATTLER (276 Německo)

Vydání

Nature Communications, London, Nature Publishing Group, 2017, 2041-1723

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 12.353

Kód RIV

RIV/00216224:14740/17:00100110

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1038/ncomms14635

UT WoS

000395883100001

Klíčová slova anglicky

ZELLWEGER-SYNDROME; STRUCTURAL BASIS; IDENTIFICATION; BIOGENESIS; DOCKING; SYSTEM; DOMAIN; CRYSTALLOGRAPHY; RELAXATION; COMPLEXES

Štítky

OA, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 2. 3. 2018 09:46, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

The transport of peroxisomal membrane proteins (PMPs) requires the soluble PEX19 protein as chaperone and import receptor. Recognition of cargo PMPs by the C-terminal domain (CTD) of PEX19 is required for peroxisome biogenesis in vivo. Farnesylation at a C-terminal CaaX motif in PEX19 enhances the PMP interaction, but the underlying molecular mechanisms are unknown. Here, we report the NMR-derived structure of the farnesylated human PEX19 CTD, which reveals that the farnesyl moiety is buried in an internal hydrophobic cavity. This induces substantial conformational changes that allosterically reshape the PEX19 surface to form two hydrophobic pockets for the recognition of conserved aromatic/aliphatic side chains in PMPs. Mutations of PEX19 residues that either mediate farnesyl contacts or are directly involved in PMP recognition abolish cargo binding and cannot complement a Delta PEX19 phenotype in human Zellweger patient fibroblasts. Our results demonstrate an allosteric mechanism for the modulation of protein function by farnesylation.

Návaznosti

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

EMMANOUILIDIS, L., U. SCHUTZ, Konstantinos TRIPSIANES, T. MADL, J. RADKE, R. RUCKTASCHEL, M. WILMANNS, W. SCHLIEBS, R. ERDMANN a M. SATTLER. Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19. Nature Communications. London: Nature Publishing Group, 2017, roč. 8, MAR, s. 14635-14647. ISSN 2041-1723. Dostupné z: https://dx.doi.org/10.1038/ncomms14635.

@article{1409391,
   author = {Emmanouilidis, L. and Schutz, U. and Tripsianes, Konstantinos and Madl, T. and Radke, J. and Rucktaschel, R. and Wilmanns, M. and Schliebs, W. and Erdmann, R. and Sattler, M.},
   article_location = {London},
   article_number = {MAR},
   doi = {http://dx.doi.org/10.1038/ncomms14635},
   keywords = {ZELLWEGER-SYNDROME; STRUCTURAL BASIS; IDENTIFICATION; BIOGENESIS; DOCKING; SYSTEM; DOMAIN; CRYSTALLOGRAPHY; RELAXATION; COMPLEXES},
   language = {eng},
   issn = {2041-1723},
   journal = {Nature Communications},
   title = {Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19},
   url = {https://www.nature.com/articles/ncomms14635.pdf},
   volume = {8},
   year = {2017}
}

TY  - JOUR
ID  - 1409391
AU  - Emmanouilidis, L. - Schutz, U. - Tripsianes, Konstantinos - Madl, T. - Radke, J. - Rucktaschel, R. - Wilmanns, M. - Schliebs, W. - Erdmann, R. - Sattler, M.
PY  - 2017
TI  - Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19
JF  - Nature Communications
VL  - 8
IS  - MAR
SP  - 14635
EP  - 14635
PB  - Nature Publishing Group
SN  - 20411723
KW  - ZELLWEGER-SYNDROME
KW  - STRUCTURAL BASIS
KW  - IDENTIFICATION
KW  - BIOGENESIS
KW  - DOCKING
KW  - SYSTEM
KW  - DOMAIN
KW  - CRYSTALLOGRAPHY
KW  - RELAXATION
KW  - COMPLEXES
UR  - https://www.nature.com/articles/ncomms14635.pdf
L2  - https://www.nature.com/articles/ncomms14635.pdf
N2  - The transport of peroxisomal membrane proteins (PMPs) requires the soluble PEX19 protein as chaperone and import receptor. Recognition of cargo PMPs by the C-terminal domain (CTD) of PEX19 is required for peroxisome biogenesis in vivo. Farnesylation at a C-terminal CaaX motif in PEX19 enhances the PMP interaction, but the underlying molecular mechanisms are unknown. Here, we report the NMR-derived structure of the farnesylated human PEX19 CTD, which reveals that the farnesyl moiety is buried in an internal hydrophobic cavity. This induces substantial conformational changes that allosterically reshape the PEX19 surface to form two hydrophobic pockets for the recognition of conserved aromatic/aliphatic side chains in PMPs. Mutations of PEX19 residues that either mediate farnesyl contacts or are directly involved in PMP recognition abolish cargo binding and cannot complement a Delta PEX19 phenotype in human Zellweger patient fibroblasts. Our results demonstrate an allosteric mechanism for the modulation of protein function by farnesylation.
ER  -

EMMANOUILIDIS, L., U. SCHUTZ, Konstantinos TRIPSIANES, T. MADL, J. RADKE, R. RUCKTASCHEL, M. WILMANNS, W. SCHLIEBS, R. ERDMANN a M. SATTLER. Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19. \textit{Nature Communications}. London: Nature Publishing Group, 2017, roč.~8, MAR, s.~14635-14647. ISSN~2041-1723. Dostupné z: https://dx.doi.org/10.1038/ncomms14635.

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