8HF4

Cryo-EM structure of nucleotide-bound ComA at outward-facing state with EC gate closed conformation

Summary for 8HF4

• Entry DOI: 10.2210/pdb8hf4/pdb
• EMDB information: 34712 34713 34714 34715 34716
• Descriptor: Transport/processing ATP-binding protein ComA, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER (2 entities in total)
• Functional Keywords: abc transport, pcat, membrane protein, transport protein
• Biological source: Streptococcus pneumoniae D39
• Total number of polymer chains: 2
• Total formula weight: 161912.56

Authors

Yu, L.,Xin, X.,Min, L. (deposition date: 2022-11-09, release date: 2023-10-04, Last modification date: 2024-03-06)

Primary citation

Yu, L.,Xu, X.,Chua, W.Z.,Feng, H.,Ser, Z.,Shao, K.,Shi, J.,Wang, Y.,Li, Z.,Sobota, R.M.,Sham, L.T.,Luo, M.
Structural basis of peptide secretion for Quorum sensing by ComA.
Nat Commun, 14:7178-7178, 2023

PubMed Abstract: Quorum sensing (QS) is a crucial regulatory mechanism controlling bacterial signalling and holds promise for novel therapies against antimicrobial resistance. In Gram-positive bacteria, such as Streptococcus pneumoniae, ComA is a conserved efflux pump responsible for the maturation and secretion of peptide signals, including the competence-stimulating peptide (CSP), yet its structure and function remain unclear. Here, we functionally characterize ComA as an ABC transporter with high ATP affinity and determined its cryo-EM structures in the presence or absence of CSP or nucleotides. Our findings reveal a network of strong electrostatic interactions unique to ComA at the intracellular gate, a putative binding pocket for two CSP molecules, and negatively charged residues facilitating CSP translocation. Mutations of these residues affect ComA's peptidase activity in-vitro and prevent CSP export in-vivo. We demonstrate that ATP-Mg triggers the outward-facing conformation of ComA for CSP release, rather than ATP alone. Our study provides molecular insights into the QS signal peptide secretion, highlighting potential targets for QS-targeting drugs.

PubMed: 37935699
DOI: 10.1038/s41467-023-42852-9

Experimental method

ELECTRON MICROSCOPY (2.8 Å)