title: Unique proline-rich domain regulates the chaperone function of AIPL1.
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.
authors: Center for Integrated Protein Science at the Department Chemie, Technische Universität München , Lichtenbergstrasse 4, D-85747 Garching, Germany.
authors: Jing
authors: J
authors: Li
authors: Gabriel
authors: G
authors: Zoldak
authors: Thomas
authors: T
authors: Kriehuber
authors: Joanna
authors: J
authors: Soroka
authors: Franz X
authors: FX
authors: Schmid
authors: Klaus
authors: K
authors: Richter
authors: Johannes
authors: J
authors: Buchner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002942:Circular Dichroism; D005136:Eye Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011392:Proline / Q000737:chemistry; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D020349:Surface Plasmon Resonance; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: C403625:AIPL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005136:Eye Proteins; D018841:HSP90 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; C103265:aryl hydrocarbon receptor-interacting protein; D011392:Proline; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4; D019696:Peptidylprolyl Isomerase