The peroxisomal receptor Pex19p forms a helical mPTS recognition domain.
The protein Pex19p functions as a receptor and chaperone of peroxisomal membrane proteins (PMPs). The crystal structure of the folded C-terminal part of the receptor reveals a globular domain that displays a bundle of three long helices in an antiparallel arrangement. Complementary functional experiments, using a range of truncated Pex19p constructs, show that the structured alpha-helical domain binds PMP-targeting signal (mPTS) sequences with about 10 muM affinity. Removal of a conserved N-terminal helical segment from the mPTS recognition domain impairs the ability for mPTS binding, indicating that it forms part of the mPTS-binding site. Pex19p variants with mutations in the same sequence segment abolish correct cargo import. Our data indicate a divided N-terminal and C-terminal structural arrangement in Pex19p, which is reminiscent of a similar division in the Pex5p receptor, to allow separation of cargo-targeting signal recognition and additional functions.
EMBL c/o DESY, Notkestrasse 85, Hamburg, Germany.
Nicole
N
Schueller
Simon J
SJ
Holton
Krisztian
K
Fodor
Morlin
M
Milewski
Petr
P
Konarev
Will A
WA
Stanley
Janina
J
Wolf
Ralf
R
Erdmann
Wolfgang
W
Schliebs
Young-Hwa
YH
Song
Matthias
M
Wilmanns
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D020675:Peroxisomes / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
D008565:Membrane Proteins; C087343:PEX19 protein, human