I. Introduction to Membrane Transport Proteins
II. Alternating Access of the Glucose Transporter
Part II: Alternating Access of the Glucose Transporter
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Membranes create a barrier that insulates cellular and organellar content from the surrounding environment. Some small molecules (e.g. H2O) can cross this lipid bilayer by simple diffusion, but the majority of molecules require membrane transport proteins. In this seminar, Dr. Nieng Yan explores the different mechanisms that cells have to exchange material with its environment: vesicular transport (endocytosis and exocytosis), passive transport (diffusion), and active transport (membrane proteins). Focusing on membrane channels and transporters, Yan highlights the importance of using biochemistry and structural biology to understand their function and specificity of membrane channels and transporters.
In her second talk, Yan explains how glucose transporters facilitate the intake of glucose into the cell. She explains that glucose transporters vary in localization and substrate specificity, and mutations in these proteins have been linked to health issues. Her laboratory was able to overcome the challenges of crystallizing highly mobile membrane proteins and was the first group to solve the protein structure of two glucose transporters, GLUT1 and GLUT3. Yan walks us through the discovery process and underlines how these structures allow us to grasp the substrate specificity of glucose transporters and possibly reveal potential clinical applications.
Dr. Nieng Yan is a professor in the School of Medicine at Tsinghua University, Beijing, China. After finishing her bachelor’s degree at Tsinghua University, she joined Yigong Shi’s laboratory at Princeton University, where she completed her graduate and postdoctoral training. During this time, she successfully solved the X-ray crystallography structure of several proteins involved in cell death, and started working on solving the structure of membrane proteins, a big challenge at the time. Currently, her laboratory uses a combination of structural biology and biochemistry to elucidate the mechanisms of substrate recognition and transport. Her focus and determination helped her laboratory to be the first group to solve the crystal structure of glucose transporters. Given her scientific contributions, she was selected as a HHMI International Early Career Scientist in 2012, and was awarded the Protein Science Young Investigator Award by the Protein Society and the Raymond & Beverly Sackler International Prize in Biophysics in 2015.
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Dong Deng, et. al. (2014) Crystal structure of the human glucose transporter GLUT1. Nature 510:121-5.
Dong Deng, et. al. (2015) Molecular basis of ligand recognition and transport by glucose transporters. Nature 526:391-6.
César-Razquin A, et. al. (2015) A Call for Systematic Research on Solute Carriers. Cell 162:478-87.
Yigong Shi (2013) Common folds and transport mechanisms of secondary active transporters. Annu Rev Biophys 42:51-72.
Rees DC, et. al. (2009) ABC transporters: the power to change. Nat Rev Mol Cell Biol 10:218-27.
David C. Gadsby (2009) Ion channels versus ion pumps: the principal difference, in principle. Nat Rev Mol Cell Biol 10:344-52.