4BXU

Structure of Pex14 in complex with Pex5 LVxEF motif


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Submitted: 10 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

A Novel Pex14 Interacting Site of Human Pex5 is Critical for Matrix Protein Import Into Peroxisomes.

Neuhaus, A.Kooshapur, H.Wolf, J.Meyer, H.N.Madl, T.Saidowsky, J.Hambruch, E.Lassam, A.Jung, M.Sattler, M.Schliebs, W.Erdmann, R.

(2014) J Biol Chem 289: 437

  • DOI: https://doi.org/10.1074/jbc.M113.499707
  • Primary Citation of Related Structures:  
    4BXU

  • PubMed Abstract: 

    Protein import into peroxisomes relies on the import receptor Pex5, which recognizes proteins with a peroxisomal targeting signal 1 (PTS1) in the cytosol and directs them to a docking complex at the peroxisomal membrane. Receptor-cargo docking occurs at the membrane-associated protein Pex14. In human cells, this interaction is mediated by seven conserved diaromatic penta-peptide motifs (WXXX(F/Y) motifs) in the N-terminal half of Pex5 and the N-terminal domain of Pex14. A systematic screening of a Pex5 peptide library by ligand blot analysis revealed a novel Pex5-Pex14 interaction site of Pex5. The novel motif composes the sequence LVAEF with the evolutionarily conserved consensus sequence LVXEF. Replacement of the amino acid LVAEF sequence by alanines strongly affects matrix protein import into peroxisomes in vivo. The NMR structure of a complex of Pex5-(57-71) with the Pex14-N-terminal domain showed that the novel motif binds in a similar α-helical orientation as the WXXX(F/Y) motif but that the tryptophan pocket is now occupied by a leucine residue. Surface plasmon resonance analyses revealed 33 times faster dissociation rates for the LVXEF ligand when compared with a WXXX(F/Y) motif. Surprisingly, substitution of the novel motif with the higher affinity WXXX(F/Y) motif impairs protein import into peroxisomes. These data indicate that the distinct kinetic properties of the novel Pex14-binding site in Pex5 are important for processing of the peroxisomal targeting signal 1 receptor at the peroxisomal membrane. The novel Pex14-binding site may represent the initial tethering site of Pex5 from which the cargo-loaded receptor is further processed in a sequential manner.


  • Organizational Affiliation

    From the Institut für Physiologische Chemie, Abteilung Systembiochemie, Ruhr-Universität Bochum, D-44780 Bochum.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PEROXISOMAL MEMBRANE PROTEIN PEX1469Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for O75381 (Homo sapiens)
Explore O75381 
Go to UniProtKB:  O75381
PHAROS:  O75381
GTEx:  ENSG00000142655 
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UniProt GroupO75381
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
PEROXISOMAL TARGETING SIGNAL 1 RECEPTOR15Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P50542 (Homo sapiens)
Explore P50542 
Go to UniProtKB:  P50542
PHAROS:  P50542
GTEx:  ENSG00000139197 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP50542
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Submitted: 10 

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-11-27
    Type: Initial release
  • Version 1.1: 2014-01-15
    Changes: Database references