In this section
@article{Hobbs:2025:10.1038/s41467-025-60063-2,
author = {Hobbs, B and Limmer, N and Ossa, F and Knupling, E and Lenton, S and Fodera, V and Kalverda, A and Karamanos, T},
doi = {10.1038/s41467-025-60063-2},
journal = {Nature Communications},
title = {A low-complexity linker as a driver of intra- and intermolecular interactions in DNAJB chaperones},
url = {http://dx.doi.org/10.1038/s41467-025-60063-2},
volume = {16},
year = {2025}
}
TY - JOUR
AB - J-domain proteins ( JDPs) act as major regulators of the proteostasis network by driving the specificity of the Hsp70 machine. Their important functions are mediated by a low-complexity glycine-/phenylalanine-rich region (GF-linker) that links the folded J-domain with the substrate binding domain. Recently, we and others have shown that in an autoinhibited JDP state, an α-helix formed within the GF-linker blocks the Hsp70 binding site on the J-domain. However, the role of the disordered GF-linker in autoinhibition and how the latter is released, are still not understood. Here, using autoinhibited DNAJB1 and DNAJB6 constructs, we show that in combination with the J-domain, the GF-linker creates a hydrophobic, partially collapsed cluster that shows a remarkable degree of long-range structural communication, disruption of which can lead to destabilisation of autoinhibition. Apart from this crucial intramolecular role, we reveal that the GF-linker can also be recognised by the substrate-binding domain of Hsp70 and dictate the lifetime of the entire JDP–Hsp70 complex. Strikingly, the GF-linkers of DNAJB1 and DNAJB6 display distinct structural properties that lead to different Hsp70 binding kinetics, showing that the behaviour of the GF-linker can vary dramatically even within the same class of JDPs.
AU - Hobbs,B
AU - Limmer,N
AU - Ossa,F
AU - Knupling,E
AU - Lenton,S
AU - Fodera,V
AU - Kalverda,A
AU - Karamanos,T
DO - 10.1038/s41467-025-60063-2
PY - 2025///
SN - 2041-1723
TI - A low-complexity linker as a driver of intra- and intermolecular interactions in DNAJB chaperones
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/s41467-025-60063-2
UR - https://www.nature.com/articles/s41467-025-60063-2
VL - 16
ER -
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