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Structural basis for human respiratory syncytial virus NS1-mediated modulation of host responses

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architectureHuman respiratory syncytial virus (hRSV) is a major cause of morbidity and mortality in the paediatric, elderly and immune-compromised populations. A gap in our understanding of hRSV disease pathology is the interplay between virally encoded immune antagonists and host components that limit hRSV replication. hRSV encodes for non-structural (NS) proteins that are important immune antagonists; however, the role of these proteins in viral pathogenesis is incompletely understood. Here, we report the crystal structure of hRSV NS1 protein, which suggests that NS1 is a structural paralogue of hRSV matrix (M) protein. Comparative analysis of the shared structural fold with M revealed regions unique to NS1. Studies on NS1 wild type or mutant alone or in recombinant RSVs demonstrate that structural regions unique to NS1 contribute to modulation of host responses, including inhibition of type I interferon responses, suppression of dendritic cell maturation and promotion of inflammatory responses. Transcriptional profiles of A549 cells infected with recombinant RSVs show significant differences in multiple host pathways, suggesting that NS1 may have a greater role in regulating host responses than previously appreciated. These results provide a framework to target NS1 for therapeutic development to limit hRSV-associated morbidity and mortality.

Nat Microbiol. 2017 Jun 30;2:17101.
doi: 10.1038/nmicrobiol.2017.101.

 

© 2017 Macmillan Publishers Limited.

  Chatterjee S, Luthra P, Esaulova E, Agapov E, Yen BC, Borek DM, Edwards MR, Mittal A, Jordan DS, Ramanan P, Moore ML, Pappu RV, Holtzman MJ, Artyomov MN, Basler CF, Amarasinghe GK, Leung DW.

Another SBC Highlight:

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture

 

 

Nature. 2017 Jul 27;547(7664):472-475.
doi: 10.1038/nature23269. Epub 2017 Jul 19.

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ESAF Requirements:

 

When completing your Experimental Safety Approval Form (ESAF), please include the following in your experimental description:

 

APS requests the Experimental Safety Approval Form be submitted at least seven days prior to your scheduled beamtime.

 

Failure to submit your ESAF according to this schedule may result in delaying the beginning of your experiment.

 

 

19-BM Robotic sample mounter available

 

A robot is available for use at beamline 19-BM. The sample dewar accommodates ten Unipuck magazines; pins must be 18mm in length and use either SSRL or ALS bases. Experienced users may now request remote access to 19-BM when applying for beamtime.

 

 

SBC Staff Hosting Changes

 

SBC staff are now available for User Support between the hours of 8:00am and 10:pm.

 

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Rapid Access Beamtime Available:

SBC Beamtime Request System

The on-line SBC Beamtime Request System allows users to view available beamtime on 19-ID and 19-BM, and to submit a request for rapid beamtime allocation.

Beamtime is available to the research community via a peer reviewed proposal system; it is supported by the U.S. Department of Energy, Office of Biological and Environmental Research.

Current Beamline Statistics:

APS PDB Depositions from BioSync
SBC Sector 19 2015 2016 2017 TOTAL
ID BM ID BM ID BM
PDB Depositions 259 32 216 29 131 15 5117

APS Publications Database:

Publications Total
SBC-CAT Publication List: 19-ID 1535
SBC-CAT Publication List: 19-BM 537
SBC-CAT Publication List: ALL
APS Publications Database

MCSG / APCF Announcements:

 

The Midwest Center for Structural Genomics (MCSG) is accepting applications for access to the scientific facilities and equipment available in Building #446.

 

MCSG's structure determination platform is well established, and combines technologies, robotics and expertise for gene cloning, protein production, and crystallization, as well as biochemical and biophysical characterization.

 

For further information, please contact Andrzej Joachimiak.

 

Future Meetings:

 

EMBO practical course on image processing for cryo-electron microscopy

September 05-15, 2017

London; United Kingdom

 

CSHL X-ray Methods in Structural Biology Course

October 16-31, 2017

Cold Spring Harbor; New York, USA

 

Advanced Topics in EM Structure Determination: Challenges and Opportunities

October 29 - November 03, 2017

New York; New York, USA

 

SBC Beamline Phone Numbers:

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19-ID Beamline Control Station 630-252-9823
19-ID Beamline Cordless Phone 630-252-0569
19-ID Beamline Inside D-Hutch 630-252-1819
 
19-BM Beamline Control Station 630-252-9833
19-BM Beamline Cordless Phone 630-252-0568
19-BM Beamline Inside D-Hutch 630-252-1719