Collagen IV
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
Historique:
received:
29
12
2020
revised:
11
03
2021
accepted:
24
03
2021
pubmed:
30
3
2021
medline:
21
8
2021
entrez:
29
3
2021
Statut:
ppublish
Résumé
We identified a genetic variant, an 8-residue appendage, of the α345 hexamer of collagen IV present in patients with glomerular basement membrane diseases, Goodpasture's disease and Alport syndrome, and determined the long-awaited crystal structure of the hexamer. We sought to elucidate how variants cause glomerular basement membrane disease by exploring the mechanism of the hexamer assembly. Chloride ions induced in vitro hexamer assembly in a composition-specific manner in the presence of equimolar concentrations of α3, α4, and α5 NC1 monomers. Chloride ions, together with sulfilimine crosslinks, stabilized the assembled hexamer. Furthermore, the chloride ion-dependent assembly revealed the conformational plasticity of the loop-crevice-loop bioactive sites, a critical property underlying bioactivity and pathogenesis. We explored the native mechanism by expressing recombinant α345 miniprotomers in the cell culture and characterizing the expressed proteins. Our findings revealed NC1-directed trimerization, forming protomers inside the cell; hexamerization, forming scaffolds outside the cell; and a Cl gradient-signaled hexamerization. This assembly detail, along with a crystal structure, provides a framework for understanding hexamer dysfunction. Restoration of the native conformation of bioactive sites and α345 hexamer replacement are prospective approaches to therapeutic intervention.
Identifiants
pubmed: 33775696
pii: S0021-9258(21)00372-0
doi: 10.1016/j.jbc.2021.100592
pmc: PMC8099640
pii:
doi:
Substances chimiques
Collagen Type IV
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
100592Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK018381
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK065138
Pays : United States
Organisme : NIDDK NIH HHS
ID : R24 DK103067
Pays : United States
Organisme : NIDDK NIH HHS
ID : R25 DK096999
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
Références
J Cell Sci. 2018 Apr 9;131(7):
pubmed: 29632050
J Biol Chem. 2007 Apr 6;282(14):10670-7
pubmed: 17293596
N Engl J Med. 2003 Jun 19;348(25):2543-56
pubmed: 12815141
Nat Rev Nephrol. 2021 Feb;17(2):112-127
pubmed: 32839582
J Biol Chem. 1993 Dec 15;268(35):26033-6
pubmed: 8253711
Methods Cell Biol. 2018;143:171-185
pubmed: 29310777
J Biol Chem. 2021 Jan-Jun;296:100591
pubmed: 33775698
J Biol Chem. 2000 Feb 25;275(8):6030-7
pubmed: 10681598
Kidney Int. 1982 Apr;21(4):642-52
pubmed: 7047864
J Biol Chem. 2019 May 17;294(20):7968-7981
pubmed: 30923125
J Cell Biol. 2016 May 23;213(4):479-94
pubmed: 27216258
Science. 1990 Jun 8;248(4960):1224-7
pubmed: 2349482
J Biol Chem. 2008 Dec 12;283(50):35070-7
pubmed: 18930919
J Liq Chromatogr Relat Technol. 2012 Nov;35(20):2923-2950
pubmed: 23378719
N Engl J Med. 2010 Jul 22;363(4):343-54
pubmed: 20660402
Methods Cell Biol. 2018;143:1-39
pubmed: 29310772
J Biol Chem. 2021 Jan-Jun;296:100590
pubmed: 33774048
J Biol Chem. 1987 Jun 5;262(16):7874-7
pubmed: 2438283
Biophys J. 2010 Jun 16;98(12):3004-14
pubmed: 20550913
J Biol Chem. 1990 Apr 5;265(10):5466-9
pubmed: 2318822
Am J Hum Genet. 1990 Jun;46(6):1024-33
pubmed: 2339699
Eur J Biochem. 1981 Nov;120(2):203-11
pubmed: 6274634
Science. 2009 Sep 4;325(5945):1230-4
pubmed: 19729652
J Cell Biol. 1987 Dec;105(6 Pt 1):2559-68
pubmed: 3693393
J Biol Chem. 2005 Jul 22;280(29):27147-54
pubmed: 15917228
J Biol Chem. 1985 Jul 15;260(14):8564-70
pubmed: 2409091