Embedded Files
The Hsp70:JDP System
The Hsp70:JDP System
Heat Shock Proteins of 40 kDa (Hsp40) and 70 kDa (Hsp70) are highly conserved and ubiquitous in all forms of life. They constitute an important part of the cellular “chaperome”, participating in a variety of cellular functions. Hsp40s and Hsp70s never work alone. Together, they form an obligate partnership. The defining feature of an Hsp40 is the “J-domain”, hence they are referred to as J-domain proteins (JDP). J-domain is a conserved ~70 amino acid sequence named after the canonical JDP of E. coli, DnaJ. J-domains directly interact with Hsp70’s ATPase domain and play the common, critical function of stimulating the weak intrinsic ATPase activity of their partner Hsp70’s. This allows them to regulate the chaperone functions of the Hsp70 partner. Thus JDPs are the drivers of the Hsp70 function. Although J-domains are important for JDP functions, they do not significantly contribute to their specificity. The functional specificity of a JDP primarily is determined primarily by their differential distribution in the cell and their substrate specificity. We are trying to understand the underlying mechanisms through which JDPs drive the specificity of Hsp70 machines.
JDP Network in Plants
JDP Network in Plants
Compared to Hsp70s, the number of JDPs has expanded in higher, more complex eukaryotes including plants. Although the functionality of most JDPs seems to be conserved across long evolutionary time scales, the JDP network in plants is far more complex which cannot be accounted for merely by the increased number of JDPs. Besides increasing number, regulatory differences, gene sharing, acquisition of novel moonlighting functions, and combinatorial JDP-Hsp70 and JDP-JDP interactions are driving the evolution of highly complex and robust chaperone networks in eukaryotes.
Plants possess multiple aggregate remodeling JDPs, more than even complex metazoans, humans. Their differential expression and sub-functionalized aggregate remodeling properties could be driving complex and more robust aggregate-remodeling chaperone systems in plants. Similarly, plants harbour multiple JDPs in their mitochondria as well. Their variable expression, combined with discriminate interactions between them might determine their specificity in mitochondrial protein import processes in Arabidopsis.
We are trying to understand how the emergence of complex Hsp70:JDP networks, in plants is important for growth, development, and stress tolerance.
A K Verma, P Sharma, Z Islam, A K Biswal, Y Tak, C Sahi (2024) Arabidopsis Dph4 is an Hsp70 Cochaperone with Iron-Binding Properties. ACS Omega.
Functional Specificity of J-Proteins in Budding Yeast
Functional Specificity of J-Proteins in Budding Yeast
There are thirteen JDPs in the nuclear/cytosolic compartment of Saccharomyces cerevisiae. Twelve out of these JDPs partner with the same multifunctional Hsp70 to perform diverse and often highly specialized cellular functions. Being in the same subcellular compartment, JDPs can potentially engage in fascinating interactions, both genetic as well as physical. We are trying to decipher the functional specificities of JDPs in yeast. A better insight into this network can help us understand how cells use their chaperone machinery in overseeing and fine-tuning the cellular protein quality control.
Functional Conservation and Evolution of J proteins in eukaryotes
Functional Conservation and Evolution of J proteins in eukaryotes
We are also studying the function and evolution of JDPs in more complex eukaryotes to understand how and why some JDPs have evolved to perform highly specialized and more complex cellular processes. Changes in the structure and function indicate the adaptability of JDPs to accommodate highly evolved and more complex cellular processes in higher eukaryotes. One such JDP is Cwc23 which specifically works with the spliceosome. Cwc23 is a fast-evolving JDP and its orthologs show a striking example of interolog co-evolution with their interacting partner, Ntr1, which is also an essential spliceosomal disassembly factor. We are utilizing fission yeast (Schizosaccharomyces pombe), fruit-flies (Drosophila melanogaster), and human cell lines to decipher the functional specificity and evolution of JDPs.
FUNDINGS
FUNDINGS
Page updated
Report abuse