5lnf
From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/PEX19_HUMAN PEX19_HUMAN]] Necessary for early peroxisomal biogenesis. Acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Binds and stabilizes newly synthesized PMPs in the cytoplasm by interacting with their hydrophobic membrane-spanning domains, and targets them to the peroxisome membrane by binding to the integral membrane protein PEX3. Excludes CDKN2A from the nucleus and prevents its interaction with MDM2, which results in active degradation of TP53.<ref>PMID:10051604</ref> <ref>PMID:10704444</ref> <ref>PMID:11259404</ref> <ref>PMID:11883941</ref> <ref>PMID:15007061</ref> <ref>PMID:14709540</ref> | [[http://www.uniprot.org/uniprot/PEX19_HUMAN PEX19_HUMAN]] Necessary for early peroxisomal biogenesis. Acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Binds and stabilizes newly synthesized PMPs in the cytoplasm by interacting with their hydrophobic membrane-spanning domains, and targets them to the peroxisome membrane by binding to the integral membrane protein PEX3. Excludes CDKN2A from the nucleus and prevents its interaction with MDM2, which results in active degradation of TP53.<ref>PMID:10051604</ref> <ref>PMID:10704444</ref> <ref>PMID:11259404</ref> <ref>PMID:11883941</ref> <ref>PMID:15007061</ref> <ref>PMID:14709540</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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 DeltaPEX19 phenotype in human Zellweger patient fibroblasts. Our results demonstrate an allosteric mechanism for the modulation of protein function by farnesylation. | ||
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| + | Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19.,Emmanouilidis L, Schutz U, Tripsianes K, Madl T, Radke J, Rucktaschel R, Wilmanns M, Schliebs W, Erdmann R, Sattler M Nat Commun. 2017 Mar 10;8:14635. doi: 10.1038/ncomms14635. PMID:28281558<ref>PMID:28281558</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5lnf" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 09:54, 22 March 2017
Solution NMR structure of farnesylated PEX19, C-terminal domain
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