David L. Stokes

Professor, Skirball Institute of Biomolecular Medicine, Structural Biology. Department of Cell Biology

Ph.D., 1986 Brandeis University

LAB WEBSITE:
Stokes Lab
KEYWORDS:
Membrane Transport, Electron Microscopy, Molecular Structure, Macromolecular Complexes, Cellular Dynamics

Contact Information

Skirball Institute of Biomolecular Medicine
540 First Avenue 3rd floor, Lab 13
New York, N.Y. 10016
Office Tel: (212) 263-1580
Lab Tel: (212) 263-1599
Fax: (212) 263-2150
E-mail: stokes@nyu.edu

Admin Contact

Alberta Chan
Tel: (212) 263-8573
Email: alberta.chan@nyumc.org


Electron Microscopy of Macromolecular Complexes

Our lab studies molecular mechanisms for transporting ions across the membrane as well as the architecture of complex cellular assemblies. In particular, we are using X-ray crystallography and single-particle cryo-EM to study ATP-dependent K+ transport by the Kdp complex, which is an unusual oligomeric member of the P-type ATPase family. The goals of this project are to solve the atomic structure of the protein complex and to characterize structural elements and conformational changes that are responsible for energy coupling. We are using cryo-electron microscopy to study several different secondary transporters: a Zn2+ transporter from the Cation Diffusion Facilitator family, a borate transporter from the Anion Exchange family and a citrate transporter from the Hydroxycarboxylate Transporter family. These projects rely on 2D crystals of the respective transport proteins reconstituted into a lipid bilayer. The goal is to understand the alternating access transport mechanism by revealing relevant conformational changes and by characterizing effects of mutation on in vitro functional assays. Over the past few years, we have used electron tomography to study a variety of cellular assemblies, such as the red cell cytoskeleton, the immunological synapse, desmosomes and mitochondria. For desmosomes and red cells, we have characterized the organization of the molecular scaffolds responsible for the roles these structures play in shaping cells and tissues. For mitochondria, we have revealed defects in the cristae and in the organization of F1Fo ATP-synthase that explain the pathology associated with Barth Syndrome. For immune cells, we have discovered exocytosis of microvesicles, which represents a novel response of T-cells activated by antigen recognition.

Selected Publications: 
  • Allen, G.S. Wu, C., Cardozo, T, Stokes, D.L. 2011. The Architecture of CopA from Archeaoglobus fulgidus Studied by Cryo-Electron Microscopy and Computational Docking. Structure. 19:1219-1232. PMID: 21820315
  • Nans, A., Mohandas, N., Stokes, D.L. 2011. Native ultrastructure of the red cell cytoskeleton by cryo-electron tomography. Biophys. J. 101:2341-2350. PMID: 22098732
  • Coudray N, Valvo S, Hu M, Lasala R, Kim C, Vink M, Zhou M, Provasi D, Filizola M, Tao J, Fang J, Penczek PA, Ubarretxena-Belandia I, Stokes DL. Inward-facing conformation of the zinc transporter YiiP revealed by cryoelectron microscopy. Proc Natl Acad Sci 2013 110:2140-5. PMID: 23341604
  • Choudhuri K, Llodrá J, Roth EW, Tsai J, Gordo S, Wucherpfennig KW, Kam LC, Stokes DL, Dustin ML. Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature. 2014 507:118-23. PMID: 24487619
  • Lasala R, Coudray N, Abdine A, Zhang Z, Lopez-Redondo M, Kirshenbaum R, Alexopoulos J, Zolnai Z, Stokes DL, Ubarretxena-Belandia I. Sparse and incomplete factorial matrices to screen membrane protein 2D crystallization. J Struct Biol. 2015 189:123-34. PMID: 25478971

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