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Hsp70 oligomerization is mediated by an interaction between the interdomain linker and the substrate-binding domain
- Source :
- Zaguán. Repositorio Digital de la Universidad de Zaragoza, instname, Digital.CSIC. Repositorio Institucional del CSIC, PLoS ONE, Vol 8, Iss 6, p e67961 (2013), PLoS ONE
- Publication Year :
- 2016
- Publisher :
- Public Library of Science, 2016.
-
Abstract
- Oligomerization in the heat shock protein (Hsp) 70 family has been extensively documented both in vitro and in vivo, although the mechanism, the identity of the specific protein regions involved and the physiological relevance of this process are still unclear. We have studied the oligomeric properties of a series of human Hsp70 variants by means of nanoelectrospray ionization mass spectrometry, optical spectroscopy and quantitative size exclusion chromatography. Our results show that Hsp70 oligomerization takes place through a specific interaction between the interdomain linker of one molecule and the substrate-binding domain of a different molecule, generating dimers and higher-order oligomers. We have found that substrate binding shifts the oligomerization equilibrium towards the accumulation of functional monomeric protein, probably by sequestering the helical lid sub-domain needed to stabilize the chaperone: substrate complex. Taken together, these findings suggest a possible role of chaperone oligomerization as a mechanism for regulating the availability of the active monomeric form of the chaperone and for the control of substrate binding and release. © 2013 Aprile et al.<br />FAA was recipient of a graduate fellowship from the Italian Ministry of Education, University and Research. AD is grateful for support from Murray Edwards College, Cambridge, through a Junior Research Fellowship. FS is a Sir Henry Wellcome Fellow. CR acknowledges financial support by the Spanish Ministry of Health according to the 'Plan Nacional de I+D+I 2008-2011', through ISCIII with cofunding by FEDER (CP10/00527). JLPB is a Royal Society University Research Fellow. FAA and PT are grateful for support from Regione Lombardia (NEDD and >Network Tecnologico integrato per lo studio proteomico e trascrittomico di malattie neurodegenerative correlate a deposizioni di amiloidi>). CMD acknowledges support from BBSRC (BB/E019927/1), the Wellcome Trust (094425/Z/10/Z), the European Commission (project LSHM-CT-2006-037525). NC acknowledges support from Human Frontiers Science Program (HFSP) through a Long-term Fellowship (LT000795/2009).
- Subjects :
- Spectrometry, Mass, Electrospray Ionization
lcsh:Medicine
Plasma protein binding
Polymerization
Hsp70
oligomerization
Protein–protein interaction
03 medical and health sciences
chemistry.chemical_compound
Protein structure
Heat shock protein
Humans
HSP70 Heat-Shock Proteins
Binding site
lcsh:Science
mass spectrometry
030304 developmental biology
0303 health sciences
Binding Sites
Multidisciplinary
biology
Chemistry
lcsh:R
030302 biochemistry & molecular biology
BIO/10 - BIOCHIMICA
Protein Structure, Tertiary
Monomer
Biochemistry
Chaperone (protein)
biology.protein
Biophysics
lcsh:Q
fluorescence
Linker
Molecular Chaperones
Protein Binding
Research Article
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Zaguán. Repositorio Digital de la Universidad de Zaragoza, instname, Digital.CSIC. Repositorio Institucional del CSIC, PLoS ONE, Vol 8, Iss 6, p e67961 (2013), PLoS ONE
- Accession number :
- edsair.doi.dedup.....513ef82df13eea8d9eaa5f29e6760c60