Heather Pinkett Transport and regulation of ABC transporters, virulence and multidrug resistance

Research Interests

From bacteria to mammals, ATP Binding Cassette (ABC) transporters are prevalent in many cells. ABC transporters import or export a broad spectrum of substrates, including lipids, polysaccharides, proteins or toxins across cellular membranes. With 48 known genes in the human genome, this family of membrane-spanning transport proteins plays a significant role in human disease. The ABC transporter multidrug resistance protein 1 is responsible for the resistance of tumor cells to chemotherapy, while mutations in the ABC transporter cystic fibrosis transmembrane conductance regulator (CFTR) lead to cystic fibrosis, the most frequently occurring deadly inherited disease.

My laboratory focuses on several ABC transporters to address a variety of fundamental questions that are of paramount importance; (1) how are substrates recognized during the transport process (2) how is ATP hydrolysis coupled with translocation and (3) what is the mechanism of transport for these proteins. Using a combination of crystallographic and biochemical studies, we can determine the three-dimensional structure of the molecule to understand the structural and functional roles of individual components of transporters and interactions of the whole transporter in complex with binding proteins and substrates. The ultimate goal is to capture snapshots of substrate transport as these ABC transporters pump things into or out of the cell, in hopes of controlling protein function or malfunction.

Selected Publications 

Antimicrobial Peptide Recognition Motif of the Substrate Binding Protein SapA from Nontypeable Haemophilus influenzae. Rivera KG, Tanaka KJ, Buechel ER, Origel O Jr, Harrison A, Mason KM and Pinkett HW. Biochemistry. 2024 January 08;63(3):294-311.

Activity of the pleiotropic drug resistance transcription factors Pdr1p and Pdr3p is modulated by binding site flanking sequences. Buechel ER, and Pinkett HW. FEBS Lett. 2023 October 24;598(2):169-186.

Detergent Alternatives: Membrane Protein Purification Using Synthetic Nanodisc Polymers. Dimitrova VS, Song S, Karagiaridi A, Marand A, and Pinkett HW. Methods Mol. Bio. 2022 July 01;2507:375-387.

Oligopeptide-binding protein from nontypeable Haemophilus influenzae has ligand-specific sites to accomodate peptides and heme in the binding pocket. Tanaka KJ, and Pinkett HW. J. Biol. Chem. 2019 January 18;294(3):1070-1082.

Microevolution in response to transient heme-iron restriction enhances intracellular bacterial community development and persistence. Hardison RL, Harrison A, Wallace RM, Heimlich DR, O'Bryan ME, Sebra RP, Pinkett HW, Justice SS, and Mason KM. PLoS Pathog. 2018 October 17;14(10):e1007355.

View all publications by Heather Pinkett listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.