Low sequence identity but high structural and functional conservation: The case of Hsp70/Hsp90 organizing protein (Hop/Sti1) of Leishmania braziliensis.
Parasites belonging to the genus Leishmania are subjected to extensive environmental changes during their life cycle; molecular chaperones/co-chaperones act as protagonists in this scenario to maintain cellular homeostasis. Hop/Sti1 is a co-chaperone that connects the Hsp90 and Hsp70 systems, modulating their ATPase activities and affecting the fate of client proteins because it facilitates their transfer from the Hsp70 to the Hsp90 chaperone. Hop/Sti1 is one of the most prevalent co-chaperones, highlighting its importance despite the relatively low sequence identity among orthologue proteins. This multi-domain protein comprises three tetratricopeptides domains (TPR1, TPR2A and TPR2B) and two Asp/Pro-rich domains. Given the importance of Hop/Sti1 for the chaperone system and for Leishmania protozoa viability, the Leishmania braziliensis Hop (LbHop) and a truncated mutant (LbHop(TPR2AB)) were characterized. Structurally, both proteins are α-helix-rich and highly elongated monomeric proteins. Functionally, they inhibited the ATPase activity of Leishmania braziliensis Hsp90 (LbHsp90) to a similar extent, and the thermodynamic parameters of their interactions with LbHsp90 were similar, indicating that TPR2A-TPR2B forms the functional center for the LbHop interaction with LbHsp90. These results highlight the structural and functional similarity of Hop/Sti1 proteins, despite their low sequence conservation compared to the Hsp70 and Hsp90 systems, which are phylogenetic highly conserved.
Instituto de Química de São Carlos, Universidade de São Paulo (USP), Av. Trabalhador Sãocarlense, 400 - CP 780, 13560-970, São Carlos, SP, Brazil.
Fernanda A H
FAH
Batista
Instituto de Química de São Carlos, Universidade de São Paulo (USP), Av. Trabalhador Sãocarlense, 400 - CP 780, 13560-970, São Carlos, SP, Brazil.
Thiago V
TV
Seraphim
Instituto de Química, Universidade Estadual de Campinas (UNICAMP), Rua José de Castro, s/n - Cidade Universitária - CP 6154, 13083-970, Campinas, SP, Brazil.
Clelton A
CA
Santos
Instituto de Química de São Carlos, Universidade de São Paulo (USP), Av. Trabalhador Sãocarlense, 400 - CP 780, 13560-970, São Carlos, SP, Brazil.
Marisvanda R
MR
Gonzaga
Instituto de Física, Universidade de São Paulo (USP), Av. Prof. Lineu Prestes, 748, CP 26077, São Paulo, SP, Brazil.
Leandro R S
LRS
Barbosa
Instituto de Química, Universidade Estadual de Campinas (UNICAMP), Rua José de Castro, s/n - Cidade Universitária - CP 6154, 13083-970, Campinas, SP, Brazil; Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Av. Brigadeiro Trompowsky, s/n - Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
Carlos H I
CHI
Ramos
Instituto de Química de São Carlos, Universidade de São Paulo (USP), Av. Trabalhador Sãocarlense, 400 - CP 780, 13560-970, São Carlos, SP, Brazil. Electronic address: borgesjc@iqsc.usp.br.
Júlio C
JC
Borges
D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D004789:Enzyme Activation; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D007892:Leishmania braziliensis / Q000201:enzymology*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D015800:Protozoan Proteins; C109320:stress-inducible protein 1, Leishmania major
Hop; Hsp90; L. braziliensis; Molecular chaperones; Protozoa; TPR