The Astonishing Large Family of HSP40/DnaJ Proteins Existing in Leishmania

Abstract

Abrupt environmental changes are faced by Leishmania parasites during transmission from a poikilothermic insect vector to a warm-blooded host. Adaptation to harsh environmental conditions, such as nutrient deprivation, hypoxia, oxidative stress and heat shock needs to be accomplished by rapid reconfiguration of gene expression and remodeling of protein interaction networks. Chaperones play a central role in the maintenance of cellular homeostasis, and they are responsible for crucial tasks such as correct folding of nascent proteins, protein translocation across different subcellular compartments, avoiding protein aggregates and elimination of damaged proteins. Nearly one percent of the gene content in the Leishmania genome corresponds to members of the HSP40 family, a group of proteins that assist HSP70s in a variety of cellular functions. Despite their expected relevance in the parasite biology and infectivity, little is known about their functions or partnership with the different Leishmania HSP70s. Here, we summarize the structural features of the 72 HSP40 proteins encoded in the Leishmania infantum genome and their classification into four categories. A review of proteomic data, together with orthology analyses, allow us to postulate cellular locations and possible functional roles for some of them. A detailed study of the members of this family would provide valuable information and opportunities for drug discovery and improvement of current treatments against leishmaniasis.

Linear motifs regulating protein secretion, sorting and autophagy in Leishmania parasites are diverged with respect to their host equivalents

“…The latter protein domain is a glycan-sensing module (some LysM domains bind chitin, others peptidoglycan) involved in detection and clearance of invading organisms in other eukaryotes (as a cytoplasmic sensor), although its ligand specificity in Leishmania is unclear [ 65 ]. Another interesting finding is the frequent presence of putative LIR motifs on DnaJ chaperones, a protein family highly expanded in Leishmania species [ 66 ]. DnaJ (HSP40) proteins are known to be involved in chaperone-mediated autophagy [ 67 ] therefore at least some of these motifs might have functional significance.…”

Visceral Leishmaniasis: A Case Confirmed by Metagenomic Next-Generation Sequencing from Northwestern China

“…Phylogenetic analysis using the putative chaperone protein DNAj gene fragment (corresponding to read 2 in Table S1 ) revealed that it was clustered with L. donovani within the same clade, with L. infantum, L. chagasi , and L. major as sister clades ( Figure 3 ). 9 , 10 No other pathogenic bacteria, fungi, viruses or parasites were detected. Subsequently, a positive result was obtained using an rK39 dipstick (InBios International, Seattle, WA, USA).…”

Genome-Wide Identification and Analysis of the Hsp40/J-Protein Family Reveals Its Role in Soybean (Glycine max) Growth and Development

“…The sequence files were filtered according to the following criteria: (1) select the longest transcript to denote each locus, (2) eliminate coding sequences < 150 bp, and (3) remove truncated and incomplete domain encoding genes [29]. After filtering, the sequences were submitted to a Hidden Markov Model (HMM) of a Pfam search of protein sequences to identify the protein domain family gene IDs [30], confirmed in the SMART database (http://smart.embl-heidelberg.de/) (accessed on 8 August 2022) and the National Center for Biotechnology Information (NCBI) Batch Web CD-Search Tool (https://www.ncbi.nlm.nih.gov/Structure/bwrpsb/bwrpsb.cgi) (accessed on 8 August 2022) [17].…”