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.

Basic information

Original name

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

Authors

EMMANOUILIDIS, L. (276 Germany), U. SCHUTZ (276 Germany), Konstantinos TRIPSIANES (300 Greece, guarantor, belonging to the institution), T. MADL (40 Austria), J. RADKE (276 Germany), R. RUCKTASCHEL (276 Germany), M. WILMANNS (276 Germany), W. SCHLIEBS (276 Germany), R. ERDMANN (276 Germany) and M. SATTLER (276 Germany)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 12.353

RIV identification code

RIV/00216224:14740/17:00100110

Organization unit

Central European Institute of Technology

DOI

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

UT WoS

000395883100001

Keywords in English

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

Abstract

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.

Links

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

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

Detailed Information on Publication Record