The structure of nontypeable Haemophilus influenzae SapA in a closed conformation reveals a constricted ligand-binding cavity and a novel RNA binding motif.

Nontypeable Haemophilus influenzae (NTHi) is a significant pathogen in respiratory disease and otitis media. Important for NTHi survival, colonization and persistence in vivo is the Sap (sensitivity to antimicrobial peptides) ABC transporter system. Current models propose a direct role for Sap in he...

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Autores principales:	Petra Lukacik, C David Owen, Gemma Harris, Jani Reddy Bolla, Sarah Picaud, Irfan Alibay, Joanne E Nettleship, Louise E Bird, Raymond J Owens, Philip C Biggin, Panagis Filippakopoulos, Carol V Robinson, Martin A Walsh
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3848955c7713409e903d25b26102d894
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spelling	oai:doaj.org-article:3848955c7713409e903d25b26102d8942021-12-02T20:13:40ZThe structure of nontypeable Haemophilus influenzae SapA in a closed conformation reveals a constricted ligand-binding cavity and a novel RNA binding motif.1932-620310.1371/journal.pone.0256070https://doaj.org/article/3848955c7713409e903d25b26102d8942021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256070https://doaj.org/toc/1932-6203Nontypeable Haemophilus influenzae (NTHi) is a significant pathogen in respiratory disease and otitis media. Important for NTHi survival, colonization and persistence in vivo is the Sap (sensitivity to antimicrobial peptides) 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 (Kd 282 μM) through a surface exposed histidine, while the dsRNA is coordinated via residues which constitute part of a conserved motif (estimated Kd 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.Petra LukacikC David OwenGemma HarrisJani Reddy BollaSarah PicaudIrfan AlibayJoanne E NettleshipLouise E BirdRaymond J OwensPhilip C BigginPanagis FilippakopoulosCarol V RobinsonMartin A WalshPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0256070 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Petra Lukacik C David Owen Gemma Harris Jani Reddy Bolla Sarah Picaud Irfan Alibay Joanne E Nettleship Louise E Bird Raymond J Owens Philip C Biggin Panagis Filippakopoulos Carol V Robinson Martin A Walsh The structure of nontypeable Haemophilus influenzae SapA in a closed conformation reveals a constricted ligand-binding cavity and a novel RNA binding motif.
description	Nontypeable Haemophilus influenzae (NTHi) is a significant pathogen in respiratory disease and otitis media. Important for NTHi survival, colonization and persistence in vivo is the Sap (sensitivity to antimicrobial peptides) 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 (Kd 282 μM) through a surface exposed histidine, while the dsRNA is coordinated via residues which constitute part of a conserved motif (estimated Kd 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.
format	article
author	Petra Lukacik C David Owen Gemma Harris Jani Reddy Bolla Sarah Picaud Irfan Alibay Joanne E Nettleship Louise E Bird Raymond J Owens Philip C Biggin Panagis Filippakopoulos Carol V Robinson Martin A Walsh
author_facet	Petra Lukacik C David Owen Gemma Harris Jani Reddy Bolla Sarah Picaud Irfan Alibay Joanne E Nettleship Louise E Bird Raymond J Owens Philip C Biggin Panagis Filippakopoulos Carol V Robinson Martin A Walsh
author_sort	Petra Lukacik
title	The structure of nontypeable Haemophilus influenzae SapA in a closed conformation reveals a constricted ligand-binding cavity and a novel RNA binding motif.
title_short	The structure of nontypeable Haemophilus influenzae SapA in a closed conformation reveals a constricted ligand-binding cavity and a novel RNA binding motif.
title_full	The structure of nontypeable Haemophilus influenzae SapA in a closed conformation reveals a constricted ligand-binding cavity and a novel RNA binding motif.
title_fullStr	The structure of nontypeable Haemophilus influenzae SapA in a closed conformation reveals a constricted ligand-binding cavity and a novel RNA binding motif.
title_full_unstemmed	The structure of nontypeable Haemophilus influenzae SapA in a closed conformation reveals a constricted ligand-binding cavity and a novel RNA binding motif.
title_sort	structure of nontypeable haemophilus influenzae sapa in a closed conformation reveals a constricted ligand-binding cavity and a novel rna binding motif.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/3848955c7713409e903d25b26102d894
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The structure of nontypeable Haemophilus influenzae SapA in a closed conformation reveals a constricted ligand-binding cavity and a novel RNA binding motif.

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