5LNF

Solution NMR structure of farnesylated PEX19, C-terminal domain

5LNF の概要

• エントリーDOI: 10.2210/pdb5lnf/pdb
• NMR情報: BMRB: 34030
• 分子名称: Peroxisomal biogenesis factor 19, FARNESYL (2 entities in total)
• 機能のキーワード: pex19, farnesylation, post translational modification, allostery, chaperone
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15871.01

構造登録者

Emmanouilidis, L.,Schuetz, U.,Tripsianes, K.,Madl, T.,Radke, J.,Rucktaeschel, R.,Wilmanns, M.,Schliebs, W.,Erdmann, R.,Sattler, M. (登録日: 2016-08-04, 公開日: 2017-03-15, 最終更新日: 2024-11-13)

主引用文献

Emmanouilidis, L.,Schutz, U.,Tripsianes, K.,Madl, T.,Radke, J.,Rucktaschel, R.,Wilmanns, M.,Schliebs, W.,Erdmann, R.,Sattler, M.
Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19.
Nat Commun, 8:14635-14635, 2017

PubMed Abstract: 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 ΔPEX19 phenotype in human Zellweger patient fibroblasts. Our results demonstrate an allosteric mechanism for the modulation of protein function by farnesylation.

PubMed: 28281558
DOI: 10.1038/ncomms14635

実験手法

SOLUTION NMR