Publication

Article Metrics

Citations


Online attention

Insights into bacterial lipoprotein trafficking from a structure of LolA bound to the LolC periplasmic domain

DOI: 10.1073/pnas.1806822115 DOI Help

Authors: Elise Kaplan (University of Cambridge) , Nicholas P. Greene (University of Cambridge) , Allister Crow (University of Cambridge) , Vassilis Koronakis (University of Cambridge)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 8

State: Published (Approved)
Published: July 2018

Abstract: In Gram-negative bacteria, outer-membrane lipoproteins are essential for maintaining cellular integrity, transporting nutrients, establishing infections, and promoting the formation of biofilms. The LolCDE ABC transporter, LolA chaperone, and LolB outer-membrane receptor form an essential system for transporting newly matured lipoproteins from the outer leaflet of the cytoplasmic membrane to the innermost leaflet of the outer membrane. Here, we present a crystal structure of LolA in complex with the periplasmic domain of LolC. The structure reveals how a solvent-exposed β-hairpin loop (termed the “Hook”) and trio of surface residues (the “Pad”) of LolC are essential for recruiting LolA from the periplasm and priming it to receive lipoproteins. Experiments with purified LolCDE complex demonstrate that association with LolA is independent of nucleotide binding and hydrolysis, and homology models based on the MacB ABC transporter predict that LolA recruitment takes place at a periplasmic site located at least 50 Å from the inner membrane. Implications for the mechanism of lipoprotein extraction and transfer are discussed. The LolA–LolC structure provides atomic details on a key protein interaction within the Lol pathway and constitutes a vital step toward the complete molecular understanding of this important system.

Journal Keywords: lipoprotein trafficking; protein interactions; membrane biogenesis; X-ray crystallography; ABC transporter

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography

Other Facilities: European Synchrotron Radiation Facility

Added On: 25/07/2018 08:59

Discipline Tags:

Pathogens Antibiotic Resistance Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)