Special Pharmacology Seminar: Heather W. Pinkett, Thursday 12 November

Speaker: Dr Heather W. Pinkett, Northwestern University
Series: Department of Pharmacology Seminar Series

Thursday November 12, 2026, 12:00 - 13:00

Speaker: Dr Heather W. Pinkett, Northwestern University

Talk Title: Structural and Mechanistic Studies of Bacteria ABC Transporters

Venue: Pharmacology Seminar Room

Abstract: ATP-binding cassette (ABC) transporters are ubiquitous membrane proteins that couple ATP binding and hydrolysis to the movement of substrates across cellular membranes. In bacterial pathogens, ABC transport systems contribute to nutrient acquisition, environmental adaptation, quorum sensing, biofilm formation, and resistance to host immune defenses, making them important systems for understanding bacterial physiology and potential targets for antimicrobial intervention. A central feature of many bacterial ABC importers is their interaction with substrate-binding proteins (SBPs), which recognize diverse ligands and deliver them to membrane-embedded transporter complexes.

Our work combines structural biology, biophysical approaches and computational analysis to investigate how bacterial ABC transporters recognize substrates and coordinate substrate delivery with the ATPase cycle. Studies of peptide-binding proteins illustrate the diversity of substrate-recognition mechanisms, ranging from the selective recognition of antimicrobial peptides by SapA to the broader peptide specificity of OppA. Complementary structural studies of the Type II transporter Haemophilus influenzae reveal how nucleotide state regulates SBP–transporter interactions. Cryo-electron microscopy structures captured nucleotide-dependent remodeling of the SBP, including an asymmetric partially docked state in which one SBP lobe remains engaged while interactions with the second lobe are disrupted.

Together, these studies highlight the dynamic nature of ABC transporter–SBP interactions and demonstrate how substrate recognition, transporter architecture, and nucleotide-dependent conformational changes are integrated during transport. Understanding these mechanisms provides a framework for predicting transporter function and for developing strategies to manipulate bacterial transport pathways through substrate mimics, transport inhibitors, or transporter-mediated drug delivery.