Unique proline-rich domain regulates the chaperone function of AIPL1

Jing Li; Gabriel Zoldak; Thomas Kriehuber; Joanna Soroka; Franz X Schmid; Klaus Richter; Johannes Buchner

doi:10.1021/bi301648q

Unique proline-rich domain regulates the chaperone function of AIPL1

Biochemistry. 2013 Mar 26;52(12):2089-96. doi: 10.1021/bi301648q. Epub 2013 Mar 13.

Authors

Jing Li¹, Gabriel Zoldak, Thomas Kriehuber, Joanna Soroka, Franz X Schmid, Klaus Richter, Johannes Buchner

Affiliation

¹ Center for Integrated Protein Science at the Department Chemie, Technische Universität München , Lichtenbergstrasse 4, D-85747 Garching, Germany.

PMID: 23418749
DOI: 10.1021/bi301648q

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Amino Acid Sequence
Carrier Proteins / chemistry*
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Circular Dichroism
Eye Proteins / chemistry*
Eye Proteins / genetics
Eye Proteins / metabolism*
HSP90 Heat-Shock Proteins / chemistry
HSP90 Heat-Shock Proteins / metabolism
Humans
Intracellular Signaling Peptides and Proteins / chemistry*
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism*
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

Substances

AIPL1 protein, human
Adaptor Proteins, Signal Transducing
Carrier Proteins
Eye Proteins
HSP90 Heat-Shock Proteins
Intracellular Signaling Peptides and Proteins
Molecular Chaperones
aryl hydrocarbon receptor-interacting protein
Proline
Tacrolimus Binding Proteins
tacrolimus binding protein 4
Peptidylprolyl Isomerase