Heather Pinkett Membrane proteins; emphasizing the structure & function of membrane-embedded transporters & their regulation mechanisms

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 

Selective substrate uptake: The role of ATP-binding cassette (ABC) importers in pathogenesis. Tanaka KJ, Song S, Mason K, and Pinkett HW. Biochimica et Biophysica Acta - Biomembranes. 2018 April;1860(4):868-877.

Diversity in ABC transporters: Type I, II and III importersRice AJ, Park A, and Pinkett HW. Critical Reviews in Biochemistry and Molecular Biology. 2014 September/October;49(5):426-437.

Effects of lipid environment on the conformational changes of an ABC importerRice AJ, Alvarez FJD, Davidson AL, and Pinkett HW. Channels. 2014 July/August;8(4):327-333.

Small Substrate Transport and Mechanism of a Molybdate ATP Binding Cassette Transporter in a Lipid EnvironmentRice AJ, Harrison A, Alvarez FJD, Davidson AL, and Pinkett HW. Journal of Biological Chemistry. 2014 May 23;289(21):15005-15013.

EPR Spectroscopy of MolB2C2-A Reveals Mechanism of Transport for a Bacterial Type II Molybdate ImporterRice AJ, Alvarez FJD, Schultz KM, Klug CS, Davidson AL, and Pinkett HW. Journal of Biological Chemistry. 2013 July 19;288(29):21228-21235.

Classification of a Haemophilus influenzae ABC Transporter HI1470/71 through Its Cognate Molybdate Periplasmic Binding Protein, MolATirado-Lee L, Lee A, Rees DC, and Pinkett HW. Structure. 2011 November 9;19(11):1701-1710.

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