The co-chaperone SGT of Leishmania donovani is essential for the parasite's viability

Abstract

Molecular chaperone proteins play a pivotal role in the protozoan parasite Leishmania donovani, controlling cell fate and ensuring intracellular survival. In higher eukaryotes, the so-called co-chaperone proteins are required for client protein recognition and proper function of chaperones, among them the small glutamine-rich tetratricopeptide repeat proteins (SGT) which interact with both HSP70 and HSP90 chaperones. An atypical SGT homolog is found in the L. donovani genome, encoding a protein lacking the C-terminal glutamine-rich region, normally typical for SGT family members. The gene is expressed constitutively during the life cycle and is essential for survival and/or growth of the parasites. LdSGT forms large, stable complexes that also include another putative cochaperone, HSC70 interacting protein (HIP). The gene product forms cytoplasmic clusters, matching the subcellular distribution of HIP and partly that of the major cytoplasmic chaperones, HSP70 and HSP90, reflecting a direct molecular interaction with both chaperones.

A Telomeric Cluster of Antimony Resistance Genes on Chromosome 34 of Leishmania infantum

“…We performed protein extraction under nondenaturing conditions and performed nondenaturing polyacrylamide gel electrophoresis followed by Western blotting (31,32). ARM58 and ARM56 migrated as proteins of between 55 and 60 kDa, corresponding to their predicted molecular masses (Fig.…”

“…Nondenaturing protein extraction, nondenaturing gradient gel electrophoresis, and Western blotting of the gels were performed as described previously (31,32). Briefly, 1 ϫ 10 7 L. donovani promastigotes were harvested by centrifugation, washed twice with cold PBS, and resuspended in 40 l extraction buffer (15% glycerol, 0.5 mM 1,10-phenanthroline, 10 mM Tris-HCl, pH 8.0, 70 mM KCl).…”

The Cochaperone SGTA (Small Glutamine-rich Tetratricopeptide Repeat-containing Protein Alpha) Demonstrates Regulatory Specificity for the Androgen, Glucocorticoid, and Progesterone Receptors

“…SGTA is a 34-kDa protein containing an N-terminal dimerization domain, three central tandem TPR motifs, and a C-terminal glutamine-rich domain (17)(18)(19)(20). SGTA is conserved in almost all vertebrate and invertebrate species (18,21,22) and is ubiquitously present in nearly all tissues (17). The reported effects of SGTA on androgen receptor (AR) activity are variable and conflicting in some cases.…”

Estudo estrutural e funcional da co-chaperona SGT de <i>Leishmania braziliensis</i>

“…Posteriormente, a participação da SGT em outros processos celulares, tais como a endocitose, interações com proteínas β-amilóides, receptores do hormônio do crescimento e controle da mitose e apoptose foi descrita na literatura (Fonte et al, 2002;Schantl et al, 2003;Winnefeld et al, 2006;Yin et al, 2006;Buchanan et al, 2007;Ommen et al, 2010). Sabe-se também que essa co-chaperona é responsável por mediar a associação de diversas chaperonas moleculares.…”

“…Nesse mesmo organismo, foi observado também que a Mdy2, uma proteína com um domínio ubiquitina-like, interage com o domínio N-terminal da SGT (Liou et al, 2007). Embora esteja presente em uma grande variedade de organismos, a SGT não foi encontrada em protozoários do Filo Apicomplexa, como Plasmodium falciparum (Ommen et al, 2010).…”