In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 10 ( 2021-10-15), p. e0256070-
Abstract:
Nontypeable Haemophilus influenzae (NT Hi ) is a significant pathogen in respiratory disease and otitis media. Important for NT Hi survival, colonization and persistence in vivo is the Sap ( s ensitivity to a ntimicrobial p eptides) ABC transporter system. Current models propose a direct role for Sap in heme and antimicrobial peptide (AMP) transport. Here, the crystal structure of SapA, the periplasmic component of Sap, in a closed, ligand bound conformation, is presented. Phylogenetic and cavity volume analysis predicts that the small, hydrophobic SapA central ligand binding cavity is most likely occupied by a hydrophobic di- or tri- peptide. The cavity is of insufficient volume to accommodate heme or folded AMPs. Crystal structures of SapA have identified surface interactions with heme and dsRNA. Heme binds SapA weakly (K d 282 μM) through a surface exposed histidine, while the dsRNA is coordinated via residues which constitute part of a conserved motif (estimated K d 4.4 μM). The RNA affinity falls within the range observed for characterized RNA/protein complexes. Overall, we describe in molecular-detail the interactions of SapA with heme and dsRNA and propose a role for SapA in the transport of di- or tri-peptides.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0256070
DOI:
10.1371/journal.pone.0256070.g001
DOI:
10.1371/journal.pone.0256070.g002
DOI:
10.1371/journal.pone.0256070.g003
DOI:
10.1371/journal.pone.0256070.g004
DOI:
10.1371/journal.pone.0256070.g005
DOI:
10.1371/journal.pone.0256070.g006
DOI:
10.1371/journal.pone.0256070.t001
DOI:
10.1371/journal.pone.0256070.t002
DOI:
10.1371/journal.pone.0256070.s001
DOI:
10.1371/journal.pone.0256070.s002
DOI:
10.1371/journal.pone.0256070.s003
DOI:
10.1371/journal.pone.0256070.s004
DOI:
10.1371/journal.pone.0256070.s005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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