Abstract

This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Many biological processes are exquisitely sensitive to the level of nuclear occupancy of NFATc proteins. The process of rapid nuclear import and export is regulated by an uncharacterized allosteric switch in the N-terminus of the protein, which regulates the alternate interaction between NFATc proteins and the nuclear import and export machinery. Dephosphorylation by calcineurin unmasks a nuclear localization sequence, allowing interaction with the importin complex and rapid cytoplasmic-to-nuclear translocation. Rephosphorylation in the nucleus induces another conformational change, which exposes the nuclear export sequence (NES) and allows interaction with the nuclear export receptor Crm1. We would like to characterize the mechanism of this allosteric switch by observing differences between dephosphorylated, intermediate and fully phosphorylated states of the N-terminal domain of NFAT.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-29
Application #
7722134
Study Section
Special Emphasis Panel (ZRG1-BPC-E (40))
Project Start
2008-03-01
Project End
2009-02-28
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
29
Fiscal Year
2008
Total Cost
$573
Indirect Cost

  Institution

Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Lal, Neeraj K; Nagalakshmi, Ugrappa; Hurlburt, Nicholas K et al. (2018) The Receptor-like Cytoplasmic Kinase BIK1 Localizes to the Nucleus and Regulates Defense Hormone Expression during Plant Innate Immunity. Cell Host Microbe 23:485-497.e5
Pluvinage, Benjamin; Grondin, Julie M; Amundsen, Carolyn et al. (2018) Molecular basis of an agarose metabolic pathway acquired by a human intestinal symbiont. Nat Commun 9:1043
Beyerlein, Kenneth R; Jönsson, H Olof; Alonso-Mori, Roberto et al. (2018) Ultrafast nonthermal heating of water initiated by an X-ray Free-Electron Laser. Proc Natl Acad Sci U S A 115:5652-5657
Yoshizawa, Takuya; Ali, Rustam; Jiou, Jenny et al. (2018) Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites. Cell 173:693-705.e22
Vickers, Chelsea; Liu, Feng; Abe, Kento et al. (2018) Endo-fucoidan hydrolases from glycoside hydrolase family 107 (GH107) display structural and mechanistic similarities to ?-l-fucosidases from GH29. J Biol Chem 293:18296-18308
Nguyen, Phong T; Lai, Jeffrey Y; Lee, Allen T et al. (2018) Noncanonical role for the binding protein in substrate uptake by the MetNI methionine ATP Binding Cassette (ABC) transporter. Proc Natl Acad Sci U S A 115:E10596-E10604
Aleman, Fernando; Tzarum, Netanel; Kong, Leopold et al. (2018) Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors. Proc Natl Acad Sci U S A 115:7569-7574
Herrera, Nadia; Maksaev, Grigory; Haswell, Elizabeth S et al. (2018) Elucidating a role for the cytoplasmic domain in the Mycobacterium tuberculosis mechanosensitive channel of large conductance. Sci Rep 8:14566
Dods, Robert; Båth, Petra; Arnlund, David et al. (2017) From Macrocrystals to Microcrystals: A Strategy for Membrane Protein Serial Crystallography. Structure 25:1461-1468.e2
de Vries, Robert P; Tzarum, Netanel; Peng, Wenjie et al. (2017) A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors. EMBO Mol Med 9:1314-1325

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