O processo de enovelamento é um evento importante para o tempo de vida de uma proteína, uma vez que é essencial para a função adequada da proteína e, por conseguinte, para a fisiologia celular. Enovelamento inadequado, ou mau enovelamento, pode não só conduzir à perda de função, mas também para a formação de agregados de proteína, uma associação insolúvel de polipeptídos que prejudicam a fisiologia celular, quer por si próprios ou no processo de formação. Vários processos biológicos têm evoluído para prevenir e eliminar a existência de agregados não funcionais e amiloidogênicos, uma vez que estão associados com várias patologias humanas. Chaperonas moleculares e proteínas de choque térmico são especializadas no controle de qualidade de proteínas na célula, especificamente, auxiliando o enovelamento correto, dissolução e remoção de agregados de proteína já formados. Esta última é uma função das 'disagregases', representadas principalmente pela subfamília ClpB/ Hsp104 de chaperonas moleculares, que são comuns em todos os organismos, mas, surpreendentemente, não possuem ortólogos no citosol de células de metazoários. Esta revisão tem como objetivo descrever as características das disagregases e discutir a função da Hsp104 de levedura, uma disagregase que também está envolvida na propagação e herança de príons.

The process of folding is a seminal event in the life of a protein, as it is essential for proper protein function and therefore cell physiology. Inappropriate folding, or misfolding, can not only lead to loss of function, but also to the formation of protein aggregates, an insoluble association of polypeptides that harm cell physiology, either by themselves or in the process of formation. Several biological processes have evolved to prevent and eliminate the existence of non-functional and amyloidogenic aggregates, as they are associated with several human pathologies. Molecular chaperones and heat shock proteins are specialized in controlling the quality of the proteins in the cell, specifically by aiding proper folding, and dissolution and clearance of already formed protein aggregates. The latter is a function of disaggregases, mainly represented by the ClpB/Hsp104 subfamily of molecular chaperones, that are ubiquitous in all organisms but, surprisingly, have no orthologs in the cytosol of metazoan cells. This review aims to describe the characteristics of disaggregases and to discuss the function of yeast Hsp104, a disaggregase that is also involved in prion propagation and inheritance.

Expressed Sequence Tags (ESTs) sequencing provides reliable and useful information concerning gene expression patterns in the genomic context. Our group used bioinformatics to identify and annotate 5'EST-contigs belonging to the molecular chaperones within the Eucalyptus Genome Sequencing Project Consortium (FORESTs) database. We found that 1,959 5'EST-contigs, or approximately 1.6% of the total 5'EST-contigs, encoded chaperones, emphasizing their biological importance. About 55% of the chaperones that we found were Hsp70 chaperones and its co-chaperones, 18% were Hsp90 chaperones, 15% were Hsp60 and its co-chaperone, 8% were Hsp100 chaperones, and 4% were Small Hsps. We also investigated the digital expression profile of the chaperone genes to gain information on gene expression levels in the different libraries and we found that molecular chaperones may have differential expression. The results discussed here give important hints about the role of chaperones in Eucalyptus cells.

The secretion of bacterial virulence factors and flagellar components requires the assistance of specific type III and flagellar chaperones. Standard computational annotation of the genome of Xanthomonas axonopodis pv citri, a plant pathogen that causes citrus canker, initially did not identify any genes belonging to these chaperone categories since the primary sequence homology between them was very low. However, in a search for hypothetical proteins with characteristics similar to these chaperones, we have now identified 30 chromosomal and 10 plasmidial potential genes encoding chaperones belonging to types III/IV, and flagellar secretion systems in this organism. The significance of these findings is discussed.

Algumas proteínas ao serem sintetizadas necessitam do auxílio de chaperones moleculares para seu correto enovelamento. Chaperones também estão envolvidas na dissolução de agregados protéicos, fazendo com que seu estudo seja de relevância biotecnológica e médica. Portanto, a identificação de seqüências de chaperones moleculares é uma tarefa importante. Nós usamos ferramentas de bioinformática para procurar informações geradas pelo sugarcane EST Genome Project (SUCEST) a fim de identificar e anotar chaperones e proteínas relacionas ao estresse. As seqüências do SUCEST eram anotadas como pertencentes a uma categoria de proteínas se o E-value encontrado fosse menor que 1,0e-05. Nossas anotações mostram que 4.164 seqüências 5’ EST são homólogas a chaperones moleculares, aproximadamente 1,8% de todos os 5’ EST que foram seqüenciados pelo SUCEST. Deste total, cerca de 44% pertence à família Hsp70 e suas co-chaperones, 10% à família Hsp90 e 13% à peptidil cis, trans isomerase. Do resultado da anotação, nós predizemos a existência de 156 diferentes subclasses de genes relacionados a chaperones no genoma da cana-de-açúcar. Juntos, nossos resultados apontam que os genes que codificam para estas proteínas são diversos e abundantemente expressos, o que enfatiza sua importância biológica.

Some newly synthesized proteins require the assistance of molecular chaperones for their correct folding. Chaperones are also involved in the dissolution of protein aggregates making their study significant for both biotechnology and medicine and the identification of chaperones and stress-related protein sequences in different organisms is an important task. We used bioinformatic tools to investigate the information generated by the Sugarcane Expressed Sequence Tag (SUCEST) genome project in order to identify and annotate molecular chaperones. We considered that the SUCEST sequences belonged to this category of proteins when their E-values were lower than 1.0e-05. Our annotation shows that 4,164 of the 5’ expressed sequence tag (EST) sequences were homologous to molecular chaperones, nearly 1.8% of all the 5’ ESTs sequenced during the SUCEST project. About 43% of the chaperones which we found were Hsp70 chaperones and its co-chaperones, 10% were Hsp90 chaperones and 13% were peptidyl-prolyl cis, trans isomerase. Based on the annotation results we predicted 156 different chaperone gene subclasses in the sugarcane genome. Taken together, our results indicate that genes which encode chaperones were diverse and abundantly expressed in sugarcane cells, which emphasizes their biological importance.