1. Unique proline-rich domain regulates the chaperone function of AIPL1.
- Author
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Li J, Zoldak G, Kriehuber T, Soroka J, Schmid FX, Richter K, and Buchner J
- Subjects
- Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Carrier Proteins genetics, Circular Dichroism, Eye Proteins genetics, HSP90 Heat-Shock Proteins chemistry, HSP90 Heat-Shock Proteins metabolism, Humans, Intracellular Signaling Peptides and Proteins genetics, Molecular Chaperones chemistry, Molecular Chaperones genetics, Molecular Chaperones metabolism, Molecular Sequence Data, Peptidylprolyl Isomerase chemistry, Peptidylprolyl Isomerase genetics, Peptidylprolyl Isomerase metabolism, Proline chemistry, Protein Interaction Domains and Motifs, Protein Stability, Sequence Homology, Amino Acid, Structural Homology, Protein, Surface Plasmon Resonance, Tacrolimus Binding Proteins chemistry, Tacrolimus Binding Proteins metabolism, Carrier Proteins chemistry, Carrier Proteins metabolism, Eye Proteins chemistry, Eye Proteins metabolism, Intracellular Signaling Peptides and Proteins chemistry, Intracellular Signaling Peptides and Proteins metabolism
- Abstract
Human aryl hydrocarbon receptor (AHR) interacting protein (AIP) and AIP like 1 (AIPL1) are cochaperones of Hsp90 which share 49% sequence identity. Both proteins contain an N-terminal FKBP-like prolyl peptidyl isomerase (PPIase) domain followed by a tetratricopeptide repeat (TPR) domain. In addition, AIPL1 harbors a unique C-terminal proline-rich domain (PRD). Little is known about the functional relevance of the individual domains and how these contribute to the association with Hsp90. In this study, we show that these cochaperones differ from other Hsp90-associated PPIase as their FKBP domains are enzymatically inactive. Furthermore, in contrast to other large PPIases, AIP is inactive as a chaperone. AIPL1, however, exhibits chaperone activity and prevents the aggregation of non-native proteins. The unique proline-rich domain of AIPL1 is important for its chaperone function as its truncation severely affects the ability of AIPL1 to bind non-native proteins. Furthermore, the proline-rich domain decreased the affinity of AIPL1 for Hsp90, implying that this domain acts as a negative regulator of the Hsp90 interaction besides being necessary for efficient binding of AIPL1 to non-native proteins.
- Published
- 2013
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