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Title: Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression

Authors:
; ; ; ; ; ; ; ; ;  [1];  [2];  [2];  [2];  [2]
  1. U of Tokyo
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIHNIAID
OSTI Identifier:
1252764
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Virology; Journal Volume: 90; Journal Issue: (4) ; 02, 2016
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Oda, Shun-ichiro, Noda, Takeshi, Wijesinghe, Kaveesha J., Halfmann, Peter, Bornholdt, Zachary A., Abelson, Dafna M., Armbrust, Tammy, Stahelin, Robert V., Kawaoka, Yoshihiro, Saphire, Erica Ollmann, UW), Indiana-Med), Notre), and Scripps). Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression. United States: N. p., 2016. Web. doi:10.1128/JVI.01597-15.
Oda, Shun-ichiro, Noda, Takeshi, Wijesinghe, Kaveesha J., Halfmann, Peter, Bornholdt, Zachary A., Abelson, Dafna M., Armbrust, Tammy, Stahelin, Robert V., Kawaoka, Yoshihiro, Saphire, Erica Ollmann, UW), Indiana-Med), Notre), & Scripps). Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression. United States. doi:10.1128/JVI.01597-15.
Oda, Shun-ichiro, Noda, Takeshi, Wijesinghe, Kaveesha J., Halfmann, Peter, Bornholdt, Zachary A., Abelson, Dafna M., Armbrust, Tammy, Stahelin, Robert V., Kawaoka, Yoshihiro, Saphire, Erica Ollmann, UW), Indiana-Med), Notre), and Scripps). 2016. "Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression". United States. doi:10.1128/JVI.01597-15.
@article{osti_1252764,
title = {Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression},
author = {Oda, Shun-ichiro and Noda, Takeshi and Wijesinghe, Kaveesha J. and Halfmann, Peter and Bornholdt, Zachary A. and Abelson, Dafna M. and Armbrust, Tammy and Stahelin, Robert V. and Kawaoka, Yoshihiro and Saphire, Erica Ollmann and UW) and Indiana-Med) and Notre) and Scripps)},
abstractNote = {},
doi = {10.1128/JVI.01597-15},
journal = {Journal of Virology},
number = (4) ; 02, 2016,
volume = 90,
place = {United States},
year = 2016,
month = 7
}
  • ABSTRACT Marburg virus (MARV) is a highly pathogenic filovirus that is classified in a genus distinct from that of Ebola virus (EBOV) (generaMarburgvirusandEbolavirus, respectively). Both viruses produce a multifunctional protein termed VP35, which acts as a polymerase cofactor, a viral protein chaperone, and an antagonist of the innate immune response. VP35 contains a central oligomerization domain with a predicted coiled-coil motif. This domain has been shown to be essential for RNA polymerase function. Here we present crystal structures of the MARV VP35 oligomerization domain. These structures and accompanying biophysical characterization suggest that MARV VP35 is a trimer. In contrast, EBOVmore » VP35 is likely a tetramer in solution. Differences in the oligomeric state of this protein may explain mechanistic differences in replication and immune evasion observed for MARV and EBOV. IMPORTANCEMarburg virus can cause severe disease, with up to 90% human lethality. Its genome is concise, only producing seven proteins. One of the proteins, VP35, is essential for replication of the viral genome and for evasion of host immune responses. VP35 oligomerizes (self-assembles) in order to function, yet the structure by which it assembles has not been visualized. Here we present two crystal structures of this oligomerization domain. In both structures, three copies of VP35 twist about each other to form a coiled coil. This trimeric assembly is in contrast to tetrameric predictions for VP35 of Ebola virus and to known structures of homologous proteins in the measles, mumps, and Nipah viruses. Distinct oligomeric states of the Marburg and Ebola virus VP35 proteins may explain differences between them in polymerase function and immune evasion. These findings may provide a more accurate understanding of the mechanisms governing VP35's functions and inform the design of therapeutics.« less
  • No abstract prepared.
  • Muscle contraction and relaxation is regulated by transient elevations of myoplasmic Ca{sup 2+}. Ca{sup 2+} is released from stores in the lumen of the sarco(endo)plasmic reticulum (SER) to initiate formation of the Ca{sup 2+} transient by activation of a class of Ca{sup 2+} release channels referred to as ryanodine receptors (RyRs) and is pumped back into the SER lumen by Ca{sup 2+}-ATPases (SERCAs) to terminate the Ca{sup 2+} transient. Mutations in the type 1 ryanodine receptor gene, RYR1, are associated with 2 skeletal muscle disorders, malignant hyperthermia (MH), and central core disease (CCD). The evaluation of proposed mechanisms by whichmore » RyR1 mutations cause MH and CCD is hindered by the lack of high-resolution structural information. Here, we report the crystal structure of the N-terminal 210 residues of RyR1 (RyR{sub NTD}) at 2.5 {angstrom}. The RyR{sub NTD} structure is similar to that of the suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor (IP3Rsup), but lacks most of the long helix-turn-helix segment of the 'arm' domain in IP3Rsup. The N-terminal {beta}-trefoil fold, found in both RyR and IP{sub 3}R, is likely to play a critical role in regulatory mechanisms in this channel family. A disease-associated mutation 'hot spot' loop was identified between strands 8 and 9 in a highly basic region of RyR1. Biophysical studies showed that 3 MH-associated mutations (C36R, R164C, and R178C) do not adversely affect the global stability or fold of RyRNTD, supporting previously described mechanisms whereby mutations perturb protein-protein interactions.« less
  • Highlights: • Crystal structure of the C-terminal (CT) domain of Swt1 was determined at 2.3 Å. • Structure of the CT domain was identified as HEPN domain superfamily member. • Low-resolution envelope of Swt1 full-length in solution was analyzed by SAXS. • The middle and CT domains gave good fit to SAXS structural model. - Abstract: Swt1 is an RNA endonuclease that plays an important role in quality control of nuclear messenger ribonucleoprotein particles (mRNPs) in eukaryotes; however, its structural details remain to be elucidated. Here, we report the crystal structure of the C-terminal (CT) domain of Swt1 from Saccharomycesmore » cerevisiae, which shares common characteristics of higher eukaryotes and prokaryotes nucleotide binding (HEPN) domain superfamily. To study in detail the full-length protein structure, we analyzed the low-resolution architecture of Swt1 in solution using small angle X-ray scattering (SAXS) method. Both the CT domain and middle domain exhibited a good fit upon superimposing onto the molecular envelope of Swt1. Our study provides the necessary structural information for detailed analysis of the functional role of Swt1, and its importance in the process of nuclear mRNP surveillance.« less