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High-resolution crystal structure of arthropod Eiger TNF suggests a mode of receptor engagement and altered surface charge within endosomes

Abstract:

The tumour necrosis factor alpha (TNFα) superfamily of proteins are critical in numerous biological processes, such as in development and immunity. Eiger is the sole TNFα member described in arthropods such as in the important model organism Drosophila. To date there are no structural data on any Eiger protein. Here we present the structure of the TNF domain of Eiger from the fall armyworm Spodoptera frugiperda (SfEiger) to 1.7 Å from a serendipitously obtained crystal without prior knowledge of the protein sequence. Our structure confirms that canonical trimerization is conserved from ancestral TNFs and points towards a mode of receptor engagement. Furthermore, we observe numerous surface histidines on SfEiger, potentially acting as pH switches following internalization into endosomes. Our data contributes to the genome annotation of S. frugiperda, a voracious agricultural pest, and can serve as a basis for future structure-function investigations of the TNF system in related arthropods such as Drosophila.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s42003-019-0541-0

Authors


More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM
Sub department:
Structural Biology
Role:
Author
ORCID:
0000-0002-6336-6769
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM
Sub department:
Structural Biology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Biology
Oxford college:
New College
Role:
Author
ORCID:
0000-0001-9698-0389
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM
Sub department:
Structural Biology
Role:
Author



Publisher:
Nature Research
Journal:
Communications biology More from this journal
Volume:
2
Article number:
293
Publication date:
2019-08-06
Acceptance date:
2019-07-15
DOI:
EISSN:
2399-3642
Pmid:
31396573


Language:
English
Keywords:
Pubs id:
pubs:1041809
UUID:
uuid:9b3b28b6-7389-42cc-a89f-91cc98f2a41c
Local pid:
pubs:1041809
Source identifiers:
1041809
Deposit date:
2019-09-11

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