title: RPA-1 from Leishmania amazonensis (LaRPA-1) structurally differs from other eukaryote RPA-1 and interacts with telomeric DNA via its N-terminal OB-fold domain.
abstract: Replication protein A-1 (RPA-1) is a single-stranded DNA-binding protein involved in DNA metabolism. We previously demonstrated the interaction between LaRPA-1 and telomeric DNA. Here, we expressed and purified truncated mutants of LaRPA-1 and used circular dichroism measurements and molecular dynamics simulations to demonstrate that the tertiary structure of LaRPA-1 differs from human and yeast RPA-1. LaRPA-1 interacts with telomeric ssDNA via its N-terminal OB-fold domain, whereas RPA from higher eukaryotes show different binding modes to ssDNA. Our results show that LaRPA-1 is evolutionary distinct from other RPA-1 proteins and can potentially be used for targeting trypanosomatid telomeres.
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Botucatu, SP 18618-970, Brazil.
authors.forename: R S
authors.initials: RS
authors.lastname: Pavani
authors.affiliation: Departamento de Física e Biofísica, Instituto de Biociências, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Botucatu, SP 18618-970, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Fernandes
authors.affiliation: Laboratório Nacional de Biociências - LNBio, Centro Nacional de Pesquisa em Energia e Materiais - CNPEM, Campinas, SP 13083-970, Brazil.
authors.forename: A M
authors.initials: AM
authors.lastname: Perez
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA, USA.
authors.forename: E J R
authors.initials: EJ
authors.lastname: Vasconcelos
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, 9500 Gilman Dr, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Siqueira-Neto
authors.affiliation: Departamento de Física e Biofísica, Instituto de Biociências, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Botucatu, SP 18618-970, Brazil.
authors.forename: M R
authors.initials: MR
authors.lastname: Fontes
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Botucatu, SP 18618-970, Brazil. Electronic address: micano@ibb.unesp.br.
authors.forename: M I N
authors.initials: MI
authors.lastname: Cano
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D004277:DNA, Single-Stranded / Q000378:metabolism*; D006801:Humans; D007891:Leishmania; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism*; D051716:Replication Protein A / Q000737:chemistry* / Q000378:metabolism*; D013045:Species Specificity; D016615:Telomere / Q000235:genetics*
chemical_list: D004277:DNA, Single-Stranded; D009841:Oligonucleotides; D009844:Oligosaccharides; D015800:Protozoan Proteins; D051716:Replication Protein A
keywords: LaRPA-1; Leishmania amazonensis; OB-fold domain; Replication factor 1; Replication protein A subunit 70kDa; Telomeres