Function, evolution, and structure of J-domain proteins

Abstract

Hsp70 chaperone systems are very versatile machines present in nearly all living organisms and in nearly all intracellular compartments. They function in many fundamental processes through their facilitation of protein (re)folding, trafficking, remodeling, disaggregation, and degradation. Hsp70 machines are regulated by co-chaperones. J-domain containing proteins (JDPs) are the largest family of Hsp70 co-chaperones and play a determining role functionally specifying and directing Hsp70 functions. Many features of JDPs are not understood; however, a number of JDP experts gathered at a recent CSSI-sponsored workshop in Gdansk (Poland) to discuss various aspects of J-domain protein function, evolution, and structure. In this report, we present the main findings and the consensus reached to help direct future developments in the field of Hsp70 research.

Coessential Genetic Networks Reveal the Organization and Constituents of a Dynamic Cellular Stress Response

“…For example, within the chaperone network, we observe clusters distinguished both by subcellular localization and by patterns of induction in response to mechanistically distinct proteotoxic stresses. Of note, many chaperone and co-chaperone genes still have unresolved functional partners and localization, particularly within the HSP40/JDP family (Kampinga et al, 2019). Our network corroborates recent reports revealing the localization of individual JDPs, such as DNAJB11 in the ER lumen (Chen et al, 2017) and DNAJC11 at the inner mitochondrial membrane (Ioakeimidis et al, 2014).…”

Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results

“…The J-domain proteins (JDPs), also known as the J-protein or the Hsp40 family, are cochaperones of the ubiquitous HSPA (Hsp70) chaperones [21,22]. The human genome encodes 50 members of the family [23], and these are traditionally divided to class I (DNAJA), class II (DNAJB), and class III (DNAJC) based on their domain structure [22]. The defining feature of JDPs is the J domain (JD), which interacts with the HSPA chaperones through the conserved His-Pro-Asp (HPD) motif [22].…”

“…In the DNAJA and DNAJB classes, the N-terminal J domain is followed by a glycine/phenylalanine-rich (G/F) region, which may play different functional roles in different JDPs [22,24]. Based on data from diverse family members, the G/F region may modulate HSPA client binding [25], participate in some client interactions [26], and regulate the HSPA chaperone cycle [27,28].…”

“…Some members of both classes also contain a C-terminal dimerization domain [21,29]. The DNAJC class-a trash bin for all the JDPs lacking the G/F region and actually the largest class-is structurally and functionally divergent and includes some JDPs with highly specialized functions [21,22,29].…”

Obtenção da co-chaperona mitocondrial hDjC20 humana

“…A extremidade C-terminal apresenta um domínio de dimerização, e sua função é aumentar a afinidade com a proteína cliente (CHEETHAM; CAPLAN, 1998;KAMPINGA et al, 2018).…”