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. Issue 24 (15th November 2014)

• Record Type: Journal Article
• Authors: Pavani, R.S.; Fernandes, C.; Perez, A.M.; Vasconcelos, E.J.R.; Siqueira-Neto, J.L.; Fontes, M.R.; Cano, M.I.N.
• Is Part Of: FEBS letters. Volume 588:Issue 24(2014)
• Page Start: 4740
• Page End: 4748
• Publication Date: 2014-11-15
• Subjects: CD -- circular dichroism -- DBD -- DNA binding domain -- OBF domain -- oligonucleotide–oligosaccharide fold domain -- Rfa1 -- replication factor 1 -- RPA-1 -- replication protein A subunit 1 -- RPA70 -- replication protein A subunit 70 kDa -- ssDNA -- single-stranded DNA -- LaRPA-1 -- Leishmania amazonensis -- Telomeres -- OB-fold domain -- Replication protein A subunit 70 kDa -- Replication factor 1; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.11.005
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : LaRPA‐1 interacts with telomeric DNA only by its N‐terminal OBF domain. LaRPA‐1 in silico models differs on tertiary structure compared to human and yeast RPA‐1. LaRPA‐1 presents higher flexibility between OB‐fold domains than human RPA‐1. Yeast Rfa1 DBDs in silico models provided relevant information about RPA‐1 evolution. LaRPA‐1 is acandidate to Leishmania telomere end‐binding protein (TEP).