YPXL/I is a protein interaction motif recognized by aspergillus PalA and its human homologue, AIP1/Alix.
The zinc finger transcription factor PacC undergoes two-step proteolytic activation in response to alkaline ambient pH. PalA is a component of the fungal ambient pH signal transduction pathway. Its mammalian homologue AIP1/Alix interacts with the apoptosis-linked protein ALG-2. We show that both PalA and AIP1/Alix recognize a protein-protein binding motif that we denote YPXL/I, where Tyr, Pro, and Leu/Ile are crucial for its interactive properties. Two such motifs flanking the signaling protease cleavage site mediate direct binding of PalA to PacC, required for the first and only pH-regulated cleavage of this transcription factor. PalA can bind the "closed" (i.e., wild-type full-length) conformer of PacC, suggesting that PalA binding constitutes the first stage in the two-step proteolytic cascade, recruiting or facilitating access of the signaling protease, presumably PalB. In addition to recognizing YPXL/I motifs, both PalA and AIP1/Alix interact with the Aspergillus class E Vps protein Vps32 homologue, a member of a protein complex involved in the early steps of the multivesicular body pathway, suggesting that this interaction is an additional feature of proteins of the PalA/AIP1/Alix family.
Vincent
Olivier
O
Departamento de Microbiología Molecular, Centro de Investigaciones Biológicas del CSIC, Madrid 28006, Spain. ovincent@cib.csic.es
Rainbow
Lynne
L
Tilburn
Joan
J
Arst
Herbert N
HN
Peñalva
Miguel A
MA
D000483:Alleles; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017209:Apoptosis; D001233:Aspergillus nidulans / Q000378:metabolism*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D008954:Models, Biological; D008969:Molecular Sequence Data; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; C104643:PALA protein, Emericella nidulans; C117020:PDCD6IP protein, human; C092394:PacC protein, Aspergillus; D014157:Transcription Factors; D005982:Glutathione Transferase