Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/87375
Title: Structural modelling of the DNAJB6 oligomeric chaperone shows a peptide-binding cleft lined with conserved S/T-residues at the dimer interface
Authors: Söderberg, Christopher A. G.
Månsson, Cecilia
Bernfur, Katja
Rutsdottir, Gudrun
Härmark, Johan
Rajan, Sreekanth
Al-Karadaghi, Salam
Rasmussen, Morten
Höjrup, Peter
Hebert, Hans
Emanuelsson, Cecilia
Keywords: Chaperones
Small-angle X-ray Scattering (SAXS)
Issue Date: 2018
Source: Söderberg, C. A. G., Månsson, C., Bernfur, K., Rutsdottir, G., Härmark, J., Rajan, S., et al. (2018). Structural modelling of the DNAJB6 oligomeric chaperone shows a peptide-binding cleft lined with conserved S/T-residues at the dimer interface. Scientific Reports, 8(1), 5199-.
Series/Report no.: Scientific Reports
Abstract: The remarkably efficient suppression of amyloid fibril formation by the DNAJB6 chaperone is dependent on a set of conserved S/T-residues and an oligomeric structure, features unusual among DNAJ chaperones. We explored the structure of DNAJB6 using a combination of structural methods. Lysine-specific crosslinking mass spectrometry provided distance constraints to select a homology model of the DNAJB6 monomer, which was subsequently used in crosslink-assisted docking to generate a dimer model. A peptide-binding cleft lined with S/T-residues is formed at the monomer-monomer interface. Mixed isotope crosslinking showed that the oligomers are dynamic entities that exchange subunits. The purified protein is well folded, soluble and composed of oligomers with a varying number of subunits according to small-angle X-ray scattering (SAXS). Elongated particles (160 × 120 Å) were detected by electron microscopy and single particle reconstruction resulted in a density map of 20 Å resolution into which the DNAJB6 dimers fit. The structure of the oligomer and the S/T-rich region is of great importance for the understanding of the function of DNAJB6 and how it can bind aggregation-prone peptides and prevent amyloid diseases.
URI: https://hdl.handle.net/10356/87375
http://hdl.handle.net/10220/45394
ISSN: 2045-2322
DOI: http://dx.doi.org/10.1038/s41598-018-23035-9
Rights: © 2018 The Author(s) (Nature Publishing Group). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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