TY - JOUR

T1 - Another look at the mechanism involving trimeric dUTPases in Staphylococcus aureus pathogenicity island induction involves novel players in the party

AU - Maiques, Elisa

AU - Quiles-Puchalt, Nuria

AU - Donderis, Jorge

AU - Ciges-Tomas, J Rafael

AU - Alite, Christian

AU - Bowring, Janine Z

AU - Humphrey, Suzanne

AU - Penadés, José R

AU - Marina, Alberto

N1 - © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2016/6/20

Y1 - 2016/6/20

N2 - We have recently proposed that the trimeric staphylococcal phage encoded dUTPases (Duts) are signaling molecules that act analogously to eukaryotic G-proteins, using dUTP as a second messenger. To perform this regulatory role, the Duts require their characteristic extra motif VI, present in all the staphylococcal phage coded trimeric Duts, as well as the strongly conserved Dut motif V. Recently, however, an alternative model involving Duts in the transfer of the staphylococcal islands (SaPIs) has been suggested, questioning the implication of motifs V and VI. Here, using state-of the-art techniques, we have revisited the proposed models. Our results confirm that the mechanism by which the Duts derepress the SaPI cycle depends on dUTP and involves both motifs V and VI, as we have previously proposed. Surprisingly, the conserved Dut motif IV is also implicated in SaPI derepression. However, and in agreement with the proposed alternative model, the dUTP inhibits rather than inducing the process, as we had initially proposed. In summary, our results clarify, validate and establish the mechanism by which the Duts perform regulatory functions.

AB - We have recently proposed that the trimeric staphylococcal phage encoded dUTPases (Duts) are signaling molecules that act analogously to eukaryotic G-proteins, using dUTP as a second messenger. To perform this regulatory role, the Duts require their characteristic extra motif VI, present in all the staphylococcal phage coded trimeric Duts, as well as the strongly conserved Dut motif V. Recently, however, an alternative model involving Duts in the transfer of the staphylococcal islands (SaPIs) has been suggested, questioning the implication of motifs V and VI. Here, using state-of the-art techniques, we have revisited the proposed models. Our results confirm that the mechanism by which the Duts derepress the SaPI cycle depends on dUTP and involves both motifs V and VI, as we have previously proposed. Surprisingly, the conserved Dut motif IV is also implicated in SaPI derepression. However, and in agreement with the proposed alternative model, the dUTP inhibits rather than inducing the process, as we had initially proposed. In summary, our results clarify, validate and establish the mechanism by which the Duts perform regulatory functions.

KW - Amino Acid Motifs

KW - Amino Acid Sequence

KW - Bacterial Proteins/chemistry

KW - Binding Sites

KW - Catalytic Domain

KW - Genomic Islands

KW - Protein Binding

KW - Protein Conformation

KW - Protein Interaction Domains and Motifs

KW - Protein Multimerization

KW - Pyrophosphatases/chemistry

KW - Recombinant Fusion Proteins/metabolism

KW - Staphylococcus aureus/enzymology

KW - Structure-Activity Relationship

U2 - 10.1093/nar/gkw317

DO - 10.1093/nar/gkw317

M3 - Journal article

C2 - 27112567

VL - 44

SP - 5457

EP - 5469

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 11

ER -