Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Monday Speaker Abstracts

STRUCTURAL BASIS OF LIPOPOLYSACCHARIDE BIOSYNTHESIS AND MODIFICATION Filippo Mancia ; 1 Columbia University, New York, NY, USA The outer membrane of Gram-negative bacteria has an external leaflet that is largely composed of lipopolysaccharide (LPS), which provides a selective permeation barrier, and is also the target of select antibiotics such as the last resort polymyxins. We are interested in understanding at a molecular level how LPS is assembled and is then modified to drive antibiotic resistance, processes that are mediated by specific enzymes that reside in the bacterial inner membrane. By using a structure based integrated approach which brings together single-particle cryo-electron microscopy with genetics, biochemical experiments and molecular dynamics simulations we have come - and will present - our mechanistic understanding of the last step of LPS assembly by the O-antigen ligase WaaL, and on its subsequent modification by other glycosyltransferases that neutralize its charge to prevent binding of cationic molecules such as polymyxins.

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