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Title: Biochemical and structural analysis of the interaction between  -amyloid and fibrinogen

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1354281
Report Number(s):
BNL-112797-2016-JA
Journal ID: ISSN 0006-4971
DOE Contract Number:
SC00112704
Resource Type:
Journal Article
Resource Relation:
Journal Name: Blood; Journal Volume: 128; Journal Issue: 8
Country of Publication:
United States
Language:
English

Citation Formats

Zamolodchikov, D., Berk-Rauch, H. E., Oren, D. A., Stor, D. S., Singh, P. K., Kawasaki, M., Aso, K., Strickland, S., and Ahn, H. J. Biochemical and structural analysis of the interaction between  -amyloid and fibrinogen. United States: N. p., 2016. Web. doi:10.1182/blood-2016-03-705228.
Zamolodchikov, D., Berk-Rauch, H. E., Oren, D. A., Stor, D. S., Singh, P. K., Kawasaki, M., Aso, K., Strickland, S., & Ahn, H. J. Biochemical and structural analysis of the interaction between  -amyloid and fibrinogen. United States. doi:10.1182/blood-2016-03-705228.
Zamolodchikov, D., Berk-Rauch, H. E., Oren, D. A., Stor, D. S., Singh, P. K., Kawasaki, M., Aso, K., Strickland, S., and Ahn, H. J. 2016. "Biochemical and structural analysis of the interaction between  -amyloid and fibrinogen". United States. doi:10.1182/blood-2016-03-705228.
@article{osti_1354281,
title = {Biochemical and structural analysis of the interaction between  -amyloid and fibrinogen},
author = {Zamolodchikov, D. and Berk-Rauch, H. E. and Oren, D. A. and Stor, D. S. and Singh, P. K. and Kawasaki, M. and Aso, K. and Strickland, S. and Ahn, H. J.},
abstractNote = {},
doi = {10.1182/blood-2016-03-705228},
journal = {Blood},
number = 8,
volume = 128,
place = {United States},
year = 2016,
month = 7
}
  • The export of mRNAs is a multistep process, involving the packaging of mRNAs into messenger ribonucleoprotein particles (mRNPs), their transport through nuclear pore complexes, and mRNP remodeling events prior to translation. Ribonucleic acid export 1 (Rae1) and Nup98 are evolutionarily conserved mRNA export factors that are targeted by the vesicular stomatitis virus matrix protein to inhibit host cell nuclear export. Here, we present the crystal structure of human Rae1 in complex with the Gle2-binding sequence (GLEBS) of Nup98 at 1.65 {angstrom} resolution. Rae1 forms a seven-bladed {beta}-propeller with several extensive surface loops. The Nup98 GLEBS motif forms an {approx} 50-{angstrom}-longmore » hairpin that binds with its C-terminal arm to an essentially invariant hydrophobic surface that extends over the entire top face of the Rae1 {beta}-propeller. The C-terminal arm of the GLEBS hairpin is necessary and sufficient for Rae1 binding, and we identify a tandem glutamate element in this arm as critical for complex formation. The Rae1 {center_dot} Nup98{sup GLEBS} surface features an additional conserved patch with a positive electrostatic potential, and we demonstrate that the complex possesses single-stranded RNA-binding capability. Together, these data suggest that the Rae1 {center_dot} Nup98 complex directly binds to the mRNP at several stages of the mRNA export pathway.« less
  • Wnt association with its receptor, Frizzled (Fz), and recruitment by the latter of an adaptor, Dishevelled (Dvl), initiates signaling through at least two distinct pathways (canonical and noncanonical). Endocytosis and compartmentalization help determine the signaling outcome. Our previous work has shown that Dvl2 links at least one Frizzled family member (Fz4) to clathrin-mediated endocytosis by interacting with the {mu}2 subunit of the AP-2 clathrin adaptor, through both a classical endocytic tyrosine motif and a so-called DEP domain. We report here the crystal structure of a chimeric protein that mimics the Dvl2-{mu}2 complex. The DEP domain binds at one end ofmore » the elongated, C-terminal domain of {mu}2. This domain:domain interface shows that parts of the {mu}2 surface distinct from the tyrosine-motif site can help recruit specific receptors or adaptors into a clathrin coated pit. Mutation of residues at the DEP-{mu}2 contact or in the tyrosine motif reduce affinity of Dvl2 for {mu}2 and block efficient internalization of Fz4 in response to ligation by Wnt5a. The crystal structure has thus allowed us to identify the specific interaction that leads to Frizzled uptake and to downstream, noncanonical signaling events.« less
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