Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Neufeld, C; Filipp, FV; Simon, B; Neuhaus, A; Schüller, N; David, C; Kooshapur, H; Madl, T; Erdmann, R; Schliebs, W; Wilmanns, M; Sattler, M.
Structural basis for competitive interactions of Pex14 with the import receptors Pex5 and Pex19.
EMBO J. 2009; 28(6): 745-754.
Doi: 10.1038/emboj.2009.7
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Madl Tobias
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Protein import into peroxisomes depends on a complex and dynamic network of protein-protein interactions. Pex14 is a central component of the peroxisomal import machinery and binds the soluble receptors Pex5 and Pex19, which have important function in the assembly of peroxisome matrix and membrane, respectively. We show that the N-terminal domain of Pex14, Pex14(N), adopts a three-helical fold. Pex5 and Pex19 ligand helices bind competitively to the same surface in Pex14(N) albeit with opposite directionality. The molecular recognition involves conserved aromatic side chains in the Pex5 WxxxF/Y motif and a newly identified F/YFxxxF sequence in Pex19. The Pex14-Pex5 complex structure reveals molecular details for a critical interaction in docking Pex5 to the peroxisomal membrane. We show that mutations of Pex14 residues located in the Pex5/Pex19 binding region disrupt Pex5 and/or Pex19 binding in vitro. The corresponding full-length Pex14 variants are impaired in peroxisomal membrane localisation in vivo, showing that the molecular interactions mediated by the N-terminal domain modulate peroxisomal targeting of Pex14.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Sequence -
- Binding Sites -
- Binding, Competitive -
- Cell Line -
- DNA Mutational Analysis -
- Humans -
- Magnetic Resonance Spectroscopy -
- Membrane Proteins - chemistry Membrane Proteins - metabolism
- Models, Molecular -
- Molecular Sequence Data -
- Mutation - genetics
- Peptides - chemistry Peptides - metabolism
- Protein Binding -
- Protein Structure, Secondary -
- Protein Transport -
- Receptors, Cytoplasmic and Nuclear - chemistry Receptors, Cytoplasmic and Nuclear - metabolism
- Repressor Proteins - chemistry Repressor Proteins - metabolism
- Solutions -
- Static Electricity -
- Structure-Activity Relationship -
- Find related publications in this database (Keywords)
- import receptor
- NMR
- peroxisome biogenesis
- peroxisomes
- structural biology