Ebola virus protein VP40 binding to Sec24c for transport to the plasma membrane.
Sec24c
VP40
binding
docking
molecular dynamics
plasma membrane
protein
Journal
Proteins
ISSN: 1097-0134
Titre abrégé: Proteins
Pays: United States
ID NLM: 8700181
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
01
07
2021
received:
29
01
2021
accepted:
16
08
2021
pubmed:
26
8
2021
medline:
15
3
2022
entrez:
25
8
2021
Statut:
ppublish
Résumé
Outbreaks of the Ebola virus (EBOV) continue to occur and while a vaccine and treatment are now available, there remains a dearth of options for those who become sick with EBOV disease. An understanding at the atomic and molecular level of the various steps in the EBOV replication cycle can provide molecular targets for disrupting the virus. An important step in the EBOV replication cycle is the transport of EBOV structural matrix VP40 protein molecules to the plasma membrane inner leaflet, which involves VP40 binding to the host cell's Sec24c protein. Though some VP40 residues involved in the binding are known, the molecular details of VP40-Sec24c binding are not known. We use various molecular computational techniques to investigate the molecular details of how EBOV VP40 binds with the Sec24c complex of the ESCRT-I pathway. We employed different docking programs to identify the VP40-binding site on Sec24c and then performed molecular dynamics simulations to determine the atomic details and binding interactions of the complex. We also investigated how the inter-protein interactions of the complex are affected upon mutations of VP40 amino acids in the Sec24c-binding region. Our results provide a molecular basis for understanding previous coimmunoprecipitation experimental studies. In addition, we found that VP40 can bind to a site on Sec24c that can also bind Sec23 and suggests that VP40 may use the COPII transport mechanism in a manner that may not need the Sec23 protein in order for VP40 to be transported to the plasma membrane.
Identifiants
pubmed: 34431571
doi: 10.1002/prot.26221
pmc: PMC8738135
mid: NIHMS1735729
doi:
Substances chimiques
SEC24C protein, human
0
VP40 protein, virus
0
Vesicular Transport Proteins
0
Viral Matrix Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
340-350Subventions
Organisme : NIAID NIH HHS
ID : R01 AI081077
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
J Virol. 2015 Jul;89(13):6695-710
pubmed: 25878114
J Virol. 2001 Jun;75(11):5205-14
pubmed: 11333902
Virology. 2001 Apr 25;283(1):1-6
pubmed: 11312656
Cell. 2003 Aug 22;114(4):497-509
pubmed: 12941277
North Clin Istanb. 2015 Apr 24;2(1):81-86
pubmed: 28058346
N Engl J Med. 2014 Oct 9;371(15):1375-8
pubmed: 24805988
Protein Sci. 2014 Nov;23(11):1519-27
pubmed: 25159197
J Comput Chem. 2005 Dec;26(16):1781-802
pubmed: 16222654
Sci Rep. 2018 Jun 27;8(1):9776
pubmed: 29950600
Protein Sci. 2016 Sep;25(9):1648-58
pubmed: 27328459
Curr Biol. 2015 Feb 16;25(4):403-12
pubmed: 25619760
J Virol. 2017 Aug 24;91(18):
pubmed: 28679754
J Infect Dis. 1999 Feb;179 Suppl 1:ix-xvi
pubmed: 9988154
Curr Opin Struct Biol. 2004 Apr;14(2):147-53
pubmed: 15093828
BMJ. 2014 Sep 08;349:g5539
pubmed: 25200068
Biochim Biophys Acta Biomembr. 2017 Oct;1859(10):2012-2020
pubmed: 28711356
J Infect Dis. 2011 Nov;204 Suppl 3:S884-91
pubmed: 21987765
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W363-7
pubmed: 15980490
J Mol Graph. 1996 Feb;14(1):33-8, 27-8
pubmed: 8744570
Proteins. 2010 Aug 1;78(10):2251-64
pubmed: 20544962
Proteins. 2012 Feb;80(2):482-9
pubmed: 22086767
Cell Host Microbe. 2008 Mar 13;3(3):168-77
pubmed: 18329616
J Phys Chem B. 2019 Oct 31;123(43):9045-9053
pubmed: 31576755
J Chem Theory Comput. 2016 Jan 12;12(1):405-13
pubmed: 26631602
Lancet. 2019 Mar 2;393(10174):889-898
pubmed: 30686586
J Virol. 1999 Mar;73(3):2333-42
pubmed: 9971816
Nucleic Acids Res. 2019 Jan 8;47(D1):D351-D360
pubmed: 30398656
J Virol. 2002 May;76(10):4855-65
pubmed: 11967302
Expert Opin Ther Targets. 2014 Feb;18(2):115-20
pubmed: 24283270
Cell. 2013 Aug 15;154(4):763-74
pubmed: 23953110
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15936-41
pubmed: 14673115
J Virol. 2007 Oct;81(20):11452-60
pubmed: 17699576
J Cell Sci. 2016 Oct 1;129(19):3597-3608
pubmed: 27539921
Bioinformatics. 2014 Jun 15;30(12):1771-3
pubmed: 24532726
Curr Opin Immunol. 2021 Aug;71:27-33
pubmed: 33873076
Elife. 2020 Oct 05;9:
pubmed: 33016878
Cell. 2003 Aug 22;114(4):483-95
pubmed: 12941276
Nat Protoc. 2017 Feb;12(2):255-278
pubmed: 28079879
EMBO J. 2008 Nov 5;27(21):2918-28
pubmed: 18843296
Nature. 2002 Sep 19;419(6904):271-7
pubmed: 12239560
Elife. 2013 Sep 17;2:e00951
pubmed: 24062940
J Comput Chem. 2013 Sep 30;34(25):2135-45
pubmed: 23832629