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Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules

PSMD9 (Proteasome Macropain non-ATPase subunit 9), a proteasomal assembly chaperone, harbors an uncharacterized PDZ-like domain. Here we report the identification of five novel interacting partners of PSMD9 and provide the first glimpse at the structure of the PDZ-domain, including the molecular det...

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Autores principales: Sangith, Nikhil, Srinivasaraghavan, Kannan, Sahu, Indrajit, Desai, Ankita, Medipally, Spandana, Somavarappu, Arun Kumar, Verma, Chandra, Venkatraman, Prasanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087146/
https://www.ncbi.nlm.nih.gov/pubmed/25009770
http://dx.doi.org/10.1016/j.fob.2014.05.005
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author Sangith, Nikhil
Srinivasaraghavan, Kannan
Sahu, Indrajit
Desai, Ankita
Medipally, Spandana
Somavarappu, Arun Kumar
Verma, Chandra
Venkatraman, Prasanna
author_facet Sangith, Nikhil
Srinivasaraghavan, Kannan
Sahu, Indrajit
Desai, Ankita
Medipally, Spandana
Somavarappu, Arun Kumar
Verma, Chandra
Venkatraman, Prasanna
author_sort Sangith, Nikhil
collection PubMed
description PSMD9 (Proteasome Macropain non-ATPase subunit 9), a proteasomal assembly chaperone, harbors an uncharacterized PDZ-like domain. Here we report the identification of five novel interacting partners of PSMD9 and provide the first glimpse at the structure of the PDZ-domain, including the molecular details of the interaction. We based our strategy on two propositions: (a) proteins with conserved C-termini may share common functions and (b) PDZ domains interact with C-terminal residues of proteins. Screening of C-terminal peptides followed by interactions using full-length recombinant proteins, we discovered hnRNPA1 (an RNA binding protein), S14 (a ribosomal protein), CSH1 (a growth hormone), E12 (a transcription factor) and IL6 receptor as novel PSMD9-interacting partners. Through multiple techniques and structural insights, we clearly demonstrate for the first time that human PDZ domain interacts with the predicted Short Linear Sequence Motif (SLIM) at the C-termini of the client proteins. These interactions are also recapitulated in mammalian cells. Together, these results are suggestive of the role of PSMD9 in transcriptional regulation, mRNA processing and editing, hormone and receptor activity and protein translation. Our proof-of-principle experiments endorse a novel and quick method for the identification of putative interacting partners of similar PDZ-domain proteins from the proteome and for discovering novel functions.
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spelling pubmed-40871462014-07-09 Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules Sangith, Nikhil Srinivasaraghavan, Kannan Sahu, Indrajit Desai, Ankita Medipally, Spandana Somavarappu, Arun Kumar Verma, Chandra Venkatraman, Prasanna FEBS Open Bio Article PSMD9 (Proteasome Macropain non-ATPase subunit 9), a proteasomal assembly chaperone, harbors an uncharacterized PDZ-like domain. Here we report the identification of five novel interacting partners of PSMD9 and provide the first glimpse at the structure of the PDZ-domain, including the molecular details of the interaction. We based our strategy on two propositions: (a) proteins with conserved C-termini may share common functions and (b) PDZ domains interact with C-terminal residues of proteins. Screening of C-terminal peptides followed by interactions using full-length recombinant proteins, we discovered hnRNPA1 (an RNA binding protein), S14 (a ribosomal protein), CSH1 (a growth hormone), E12 (a transcription factor) and IL6 receptor as novel PSMD9-interacting partners. Through multiple techniques and structural insights, we clearly demonstrate for the first time that human PDZ domain interacts with the predicted Short Linear Sequence Motif (SLIM) at the C-termini of the client proteins. These interactions are also recapitulated in mammalian cells. Together, these results are suggestive of the role of PSMD9 in transcriptional regulation, mRNA processing and editing, hormone and receptor activity and protein translation. Our proof-of-principle experiments endorse a novel and quick method for the identification of putative interacting partners of similar PDZ-domain proteins from the proteome and for discovering novel functions. Elsevier 2014-06-06 /pmc/articles/PMC4087146/ /pubmed/25009770 http://dx.doi.org/10.1016/j.fob.2014.05.005 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Sangith, Nikhil
Srinivasaraghavan, Kannan
Sahu, Indrajit
Desai, Ankita
Medipally, Spandana
Somavarappu, Arun Kumar
Verma, Chandra
Venkatraman, Prasanna
Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules
title Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules
title_full Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules
title_fullStr Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules
title_full_unstemmed Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules
title_short Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules
title_sort discovery of novel interacting partners of psmd9, a proteasomal chaperone: role of an atypical and versatile pdz-domain motif interaction and identification of putative functional modules
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087146/
https://www.ncbi.nlm.nih.gov/pubmed/25009770
http://dx.doi.org/10.1016/j.fob.2014.05.005
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