7OG0

Nontypeable Haemophillus influenzae SapA in open and closed conformations, in complex with double stranded RNA

Summary for 7OG0

• Entry DOI: 10.2210/pdb7og0/pdb
• Related: 6HHL 6HJI
• Descriptor: ABC-type transport system, periplasmic component, involved in antimicrobial peptide resistance, RNA (5'-R(P*CP*CP*CP*CP*CP*CP*CP*CP*CP*CP*GP*GP*GP*GP*GP*GP*GP*GP*G)-3'), CALCIUM ION, ... (4 entities in total)
• Functional Keywords: nthi, rna binding, peptide binding, substrate binding protein, peptide binding protein
• Biological source: Haemophilus influenzae (strain 86-028NP); More
• Total number of polymer chains: 4
• Total formula weight: 131440.99

Authors

Lukacik, P.,Owen, C.D.,Nettleship, J.E.,Bird, L.E.,Owens, R.J.,Walsh, M.A. (deposition date: 2021-05-05, release date: 2021-10-27, Last modification date: 2024-11-20)

Primary citation

Lukacik, P.,Owen, C.D.,Harris, G.,Bolla, J.R.,Picaud, S.,Alibay, I.,Nettleship, J.E.,Bird, L.E.,Owens, R.J.,Biggin, P.C.,Filippakopoulos, P.,Robinson, C.V.,Walsh, M.A.
The structure of nontypeable Haemophilus influenzae SapA in a closed conformation reveals a constricted ligand-binding cavity and a novel RNA binding motif.
Plos One, 16:e0256070-e0256070, 2021

PubMed Abstract: 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.

PubMed: 34653190
DOI: 10.1371/journal.pone.0256070

Experimental method

X-RAY DIFFRACTION (2.61 Å)