Cargando…

Conserved Distal Loop Residues in the Hsp104 and ClpB Middle Domain Contact Nucleotide-binding Domain 2 and Enable Hsp70-dependent Protein Disaggregation

The homologous hexameric AAA(+) proteins, Hsp104 from yeast and ClpB from bacteria, collaborate with Hsp70 to dissolve disordered protein aggregates but employ distinct mechanisms of intersubunit collaboration. How Hsp104 and ClpB coordinate polypeptide handover with Hsp70 is not understood. Here, w...

Descripción completa

Detalles Bibliográficos
Autores principales: DeSantis, Morgan E., Sweeny, Elizabeth A., Snead, David, Leung, Eunice H., Go, Michelle S., Gupta, Kushol, Wendler, Petra, Shorter, James
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887210/
https://www.ncbi.nlm.nih.gov/pubmed/24280225
http://dx.doi.org/10.1074/jbc.M113.520759
_version_ 1782478982840582144
author DeSantis, Morgan E.
Sweeny, Elizabeth A.
Snead, David
Leung, Eunice H.
Go, Michelle S.
Gupta, Kushol
Wendler, Petra
Shorter, James
author_facet DeSantis, Morgan E.
Sweeny, Elizabeth A.
Snead, David
Leung, Eunice H.
Go, Michelle S.
Gupta, Kushol
Wendler, Petra
Shorter, James
author_sort DeSantis, Morgan E.
collection PubMed
description The homologous hexameric AAA(+) proteins, Hsp104 from yeast and ClpB from bacteria, collaborate with Hsp70 to dissolve disordered protein aggregates but employ distinct mechanisms of intersubunit collaboration. How Hsp104 and ClpB coordinate polypeptide handover with Hsp70 is not understood. Here, we define conserved distal loop residues between middle domain (MD) helix 1 and 2 that are unexpectedly critical for Hsp104 and ClpB collaboration with Hsp70. Surprisingly, the Hsp104 and ClpB MD distal loop does not contact Hsp70 but makes intrasubunit contacts with nucleotide-binding domain 2 (NBD2). Thus, the MD does not invariably project out into solution as in one structural model of Hsp104 and ClpB hexamers. These intrasubunit contacts as well as those between MD helix 2 and NBD1 are different in Hsp104 and ClpB. NBD2-MD contacts dampen disaggregase activity and must separate for protein disaggregation. We demonstrate that ClpB requires DnaK more stringently than Hsp104 requires Hsp70 for protein disaggregation. Thus, we reveal key differences in how Hsp104 and ClpB coordinate polypeptide handover with Hsp70, which likely reflects differential tuning for yeast and bacterial proteostasis.
format Online
Article
Text
id pubmed-3887210
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher American Society for Biochemistry and Molecular Biology
record_format MEDLINE/PubMed
spelling pubmed-38872102014-01-13 Conserved Distal Loop Residues in the Hsp104 and ClpB Middle Domain Contact Nucleotide-binding Domain 2 and Enable Hsp70-dependent Protein Disaggregation DeSantis, Morgan E. Sweeny, Elizabeth A. Snead, David Leung, Eunice H. Go, Michelle S. Gupta, Kushol Wendler, Petra Shorter, James J Biol Chem Protein Structure and Folding The homologous hexameric AAA(+) proteins, Hsp104 from yeast and ClpB from bacteria, collaborate with Hsp70 to dissolve disordered protein aggregates but employ distinct mechanisms of intersubunit collaboration. How Hsp104 and ClpB coordinate polypeptide handover with Hsp70 is not understood. Here, we define conserved distal loop residues between middle domain (MD) helix 1 and 2 that are unexpectedly critical for Hsp104 and ClpB collaboration with Hsp70. Surprisingly, the Hsp104 and ClpB MD distal loop does not contact Hsp70 but makes intrasubunit contacts with nucleotide-binding domain 2 (NBD2). Thus, the MD does not invariably project out into solution as in one structural model of Hsp104 and ClpB hexamers. These intrasubunit contacts as well as those between MD helix 2 and NBD1 are different in Hsp104 and ClpB. NBD2-MD contacts dampen disaggregase activity and must separate for protein disaggregation. We demonstrate that ClpB requires DnaK more stringently than Hsp104 requires Hsp70 for protein disaggregation. Thus, we reveal key differences in how Hsp104 and ClpB coordinate polypeptide handover with Hsp70, which likely reflects differential tuning for yeast and bacterial proteostasis. American Society for Biochemistry and Molecular Biology 2014-01-10 2013-11-26 /pmc/articles/PMC3887210/ /pubmed/24280225 http://dx.doi.org/10.1074/jbc.M113.520759 Text en © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/) applies to Author Choice Articles
spellingShingle Protein Structure and Folding
DeSantis, Morgan E.
Sweeny, Elizabeth A.
Snead, David
Leung, Eunice H.
Go, Michelle S.
Gupta, Kushol
Wendler, Petra
Shorter, James
Conserved Distal Loop Residues in the Hsp104 and ClpB Middle Domain Contact Nucleotide-binding Domain 2 and Enable Hsp70-dependent Protein Disaggregation
title Conserved Distal Loop Residues in the Hsp104 and ClpB Middle Domain Contact Nucleotide-binding Domain 2 and Enable Hsp70-dependent Protein Disaggregation
title_full Conserved Distal Loop Residues in the Hsp104 and ClpB Middle Domain Contact Nucleotide-binding Domain 2 and Enable Hsp70-dependent Protein Disaggregation
title_fullStr Conserved Distal Loop Residues in the Hsp104 and ClpB Middle Domain Contact Nucleotide-binding Domain 2 and Enable Hsp70-dependent Protein Disaggregation
title_full_unstemmed Conserved Distal Loop Residues in the Hsp104 and ClpB Middle Domain Contact Nucleotide-binding Domain 2 and Enable Hsp70-dependent Protein Disaggregation
title_short Conserved Distal Loop Residues in the Hsp104 and ClpB Middle Domain Contact Nucleotide-binding Domain 2 and Enable Hsp70-dependent Protein Disaggregation
title_sort conserved distal loop residues in the hsp104 and clpb middle domain contact nucleotide-binding domain 2 and enable hsp70-dependent protein disaggregation
topic Protein Structure and Folding
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887210/
https://www.ncbi.nlm.nih.gov/pubmed/24280225
http://dx.doi.org/10.1074/jbc.M113.520759
work_keys_str_mv AT desantismorgane conserveddistalloopresiduesinthehsp104andclpbmiddledomaincontactnucleotidebindingdomain2andenablehsp70dependentproteindisaggregation
AT sweenyelizabetha conserveddistalloopresiduesinthehsp104andclpbmiddledomaincontactnucleotidebindingdomain2andenablehsp70dependentproteindisaggregation
AT sneaddavid conserveddistalloopresiduesinthehsp104andclpbmiddledomaincontactnucleotidebindingdomain2andenablehsp70dependentproteindisaggregation
AT leungeuniceh conserveddistalloopresiduesinthehsp104andclpbmiddledomaincontactnucleotidebindingdomain2andenablehsp70dependentproteindisaggregation
AT gomichelles conserveddistalloopresiduesinthehsp104andclpbmiddledomaincontactnucleotidebindingdomain2andenablehsp70dependentproteindisaggregation
AT guptakushol conserveddistalloopresiduesinthehsp104andclpbmiddledomaincontactnucleotidebindingdomain2andenablehsp70dependentproteindisaggregation
AT wendlerpetra conserveddistalloopresiduesinthehsp104andclpbmiddledomaincontactnucleotidebindingdomain2andenablehsp70dependentproteindisaggregation
AT shorterjames conserveddistalloopresiduesinthehsp104andclpbmiddledomaincontactnucleotidebindingdomain2andenablehsp70dependentproteindisaggregation