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Overview

Crystallographic Studies of Membrane Transporters

Transport of molecules across biological membranes is a crucial process essential for the livelihood of every cell. Small molecules and ions need to enter and exit cells and sub-cellular compartments where they are utilized as energy sources, used as building materials for essential cellular molecules or serve as signaling agents. Synaptic transmission is only possible because of the rounds of release and uptake of neurotransmitters. Communication between cells in an organism is mediated by release of signaling molecules, whose concentration is controlled in the intercellular space by regulated uptake. All these processes depend on the successful crossing of the polar, often charged molecules across the hydrophobic barriers of lipid membranes. Numerous membrane transporters have evolved, which utilize either ATP or energy stored in the form of ion gradients to drive transport of their substrates across membranes. The later class, so-called secondary transporters, is the focus of study in our lab. We are relying on combination of X-ray crystallography and biochemistry to understand the structure of these transporters and the molecular mechanism of substrate transport. Recently, new methodologies have been developed to facilitate structural studies of membrane proteins and we will use these advances as well as develop new approaches. Crystallography of membrane proteins is an area of research, which is only now starting to enjoy an accelerated development and as a result every new structure reveals novel folds and molecular designs. In addition, every structure generates new avenues for drug discovery both because membrane transporters may serve as access points for drugs to the intracellular spaces and because transporters themselves serve as important drug targets.

Dr. Boudker is a faculty member in the Tri-Institutional PhD Program in Chemical Biology.

Highlights

  1. 1
    Journal of the American Chemical Society · 2023
    PMID: 37023263PMCID: PMC10119980DOISenior author43 citations
  2. 2
    Nature chemical biology · 2020
    PMID: 32514183PMCID: PMC7442671DOISenior author53 citations
  3. 3
    Nature communications · 2023
    PMID: 37142617PMCID: PMC10160106DOISenior author25 citations

Publications

52 publications

Active

4 grants
  • Sub-PI
    The mechanism of allosteric modulation of glutamate transporters
    National Institute of Neurological Disorders and Stroke · 2019–2031 · via Drexel University· 2 renewals
    R01NS111767-06A1
  • MPI
    Molecular Biophysics Training Program
    National Institute of General Medical Sciences · 2020–2030Training· 2 renewals
    T32GM132081-06
  • PI
    Investigating the Biological Mechanisms and Therapeutic Relevance of the SLC1A1 Amino Acid Transporter in Kidney Cancer
    U.S. Department of Defense · 2025–2029
    HT9425-25-1-0762
  • PI
    Ion coupling, permeation, and regulation in glutamate transporters
    National Institute of Neurological Disorders and Stroke · 2024–2027
    R37NS134865-03
Completed grants (7)
  • Co-I
    Functional dynamics of glutamate transporters probed by high-speed atomic force microscopy with micro- to millisecond time resolution
    National Institute of Neurological Disorders and Stroke · 2019–2025
    R01NS110790-01A1
  • PI
    The structural dynamics of a glutamate transporter homologue
    National Institute of Neurological Disorders and Stroke · 2014–2022· 2 renewals
    R37NS085318-07
  • Sub-PI
    The spilt personality of glutamate transporters: the structural basis and physiological role of a dual function transporter/channel
    National Health and Medical Research Council · 2019–2021 · via University of Sydney
    US 194717-01
  • PI
    Conformational Ensemble of Glutamate Transporters: Structure and Ionic Modulation
    National Institute of Neurological Disorders and Stroke · 2009–2021· 2 renewals
    R01NS064357-10
  • MPI
    Conformational Dynamics of a Glutamate Transporter Homologue - Pilot Project 2
    National Institute of General Medical Sciences · 2012–2013 · via University of Chicago
    U54GM087519-03
  • PI
    Isothermal Titration Calorimeter
    NCRR · 2011–2012 · via NIH RePORTER
    S10RR026970-01A1
  • PI
    Crystallographic studies of equilibrative nucleoside transporters
    NINDS · 2009–2011 · via NIH RePORTER
    R21NS065405-02

Honors & distinctions

3 honors
  • Member · National Academy of Sciences · 2022
  • Investigator · Howard Hughes Medical Institute · 2015
  • Fellow · American Academy of Arts and Sciences

News mentions

5 PhD students · 5 Postdocs

PhD · 5