Substrate recognition by DNAJB1

Scilironi, Gaia (2022) Substrate recognition by DNAJB1. Master's Research Project 2, Biomolecular Sciences.

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Abstract

J domain proteins (JDPs) are crucial molecules in the context of the cellular chaperones system. Different JDPs present different cellular activities. Class A JDPs target misfolded monomeric proteins and small aggregates, class B JPDs mostly interact with larger aggregates, including amyloid fibrils, and the class B JDP DNAJB1 presents the unique feature of participating in the amyloid fibrils disaggregation mediated by the HSP70 chaperone machinery. DNAJB1 presents a N-terminal J-domain (JD) which is followed by the GF-rich region, two C-terminal client binding domains (CTDI and CTDII) and a dimerization domain (DD): the protein forms functional homodimers. Since client binding motifs or patterns have not been identified yet for the human JDPs, we aimed to investigate the substrate binding specificity of DNAJB1 through the screening of peptide libraries (α-synuclein, p53 and luciferase). We screened the libraries with both the full-length protein and smaller constructs carrying its different subdomains (JD-GF, CTDI-CTDII-DD, CTDI-CTDII, His-SUMOCTDI, His-SUMO-CTDII). Our aim was to identify binding motifs and patterns on DNAJB1 clients. We identified a preference to bind peptides enriched in acidic and aromatic residues for the full-length protein and the constructs carrying the substrate binding domains CTDI and CTDII.

Item Type:	Thesis (Master's Research Project 2)
Supervisor name:	Linskens, M.H.K.
Degree programme:	Biomolecular Sciences
Thesis type:	Master's Research Project 2
Language:	English
Date Deposited:	02 Sep 2022 12:45
Last Modified:	02 Sep 2022 12:45
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/28496

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