Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 11 2022
05 11 2022
Historique:
received:
23
03
2022
accepted:
19
10
2022
pubmed:
6
11
2022
medline:
9
11
2022
entrez:
6
11
2022
Statut:
epublish
Résumé
Lymphocystis disease virus-1 (LCDV-1) and several other Iridoviridae encode viral insulin/IGF-1 like peptides (VILPs) with high homology to human insulin and IGFs. Here we show that while single-chain (sc) and double-chain (dc) LCDV1-VILPs have very low affinity for the insulin receptor, scLCDV1-VILP has high affinity for IGF1R where it can antagonize human IGF-1 signaling, without altering insulin signaling. Consequently, scLCDV1-VILP inhibits IGF-1 induced cell proliferation and growth hormone/IGF-1 induced growth of mice in vivo. Cryo-electron microscopy reveals that scLCDV1-VILP engages IGF1R in a unique manner, inducing changes in IGF1R conformation that led to separation, rather than juxtaposition, of the transmembrane segments and hence inactivation of the receptor. Thus, scLCDV1-VILP is a natural peptide with specific antagonist properties on IGF1R signaling and may provide a new tool to guide development of hormonal analogues to treat cancers or metabolic disorders sensitive to IGF-1 without affecting glucose metabolism.
Identifiants
pubmed: 36335114
doi: 10.1038/s41467-022-34391-6
pii: 10.1038/s41467-022-34391-6
pmc: PMC9637144
doi:
Substances chimiques
Receptor, IGF Type 1
EC 2.7.10.1
Insulin-Like Growth Factor I
67763-96-6
Insulin
0
Peptides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
6700Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK036836
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK031036
Pays : United States
Organisme : NIDDK NIH HHS
ID : R37 DK031036
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK117967
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Structure. 2020 Jul 7;28(7):786-798.e6
pubmed: 32459985
Drug Des Devel Ther. 2018 Sep 11;12:2887-2896
pubmed: 30254418
Mol Endocrinol. 1999 Dec;13(12):2163-74
pubmed: 10598589
J Gen Virol. 2017 May;98(5):890-891
pubmed: 28555546
Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):2461-2466
pubmed: 29467286
Mol Cell Biol. 1999 May;19(5):3278-88
pubmed: 10207053
Genomics. 1999 Aug 15;60(1):50-6
pubmed: 10458910
J Clin Invest. 1990 May;85(5):1672-9
pubmed: 2159026
Protein Eng. 1996 Nov;9(11):1011-9
pubmed: 8961354
J Histochem Cytochem. 1995 Jan;43(1):11-9
pubmed: 7822759
Biol Chem. 2003 May;384(5):805-9
pubmed: 12817477
Target Oncol. 2017 Oct;12(5):571-597
pubmed: 28815409
J Biol Chem. 1992 Jul 25;267(21):15229-36
pubmed: 1634553
Science. 1982 Jan 8;215(4529):185-7
pubmed: 7031900
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
Physiol Rev. 2013 Jan;93(1):405-80
pubmed: 23303914
Mol Cell Endocrinol. 2020 Dec 1;518:111035
pubmed: 32941924
Science. 1991 Oct 25;254(5031):539-44
pubmed: 1948029
Mol Metab. 2021 Feb;44:101121
pubmed: 33220491
J Biol Chem. 2002 Oct 18;277(42):39684-95
pubmed: 12138094
Res Microbiol. 2008 Jun;159(5):367-73
pubmed: 18541415
Can Med Assoc J. 1962 Nov 17;87:1046-51
pubmed: 13967778
Gene Ther. 2010 Apr;17(4):503-10
pubmed: 19956269
J Biol Chem. 2008 Jul 25;283(30):20821-9
pubmed: 18502759
Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):531-544
pubmed: 29872004
J Biol Chem. 1994 Apr 8;269(14):10609-13
pubmed: 8144650
J Biol Chem. 1978 Apr 25;253(8):2769-76
pubmed: 632300
Elife. 2014 Sep 25;3:
pubmed: 25255214
Diabetologia. 2010 Aug;53(8):1743-53
pubmed: 20424816
Biochemistry. 1981 Dec 22;20(26):7345-50
pubmed: 6275879
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
Biochem J. 2000 May 1;347 Pt 3:771-9
pubmed: 10769182
FEBS Lett. 1978 May 15;89(2):283-6
pubmed: 658418
J Biol Chem. 2016 Jul 8;291(28):14628-38
pubmed: 27226630
Proc Natl Acad Sci U S A. 1980 Dec;77(12):7137-41
pubmed: 6938960
N Engl J Med. 1979 Nov 22;301(21):1138-42
pubmed: 492275
Pediatr Diabetes. 2000 Sep;1(3):169-77
pubmed: 15016228
Eur J Biochem. 1990 Jan 12;187(1):249-54
pubmed: 1688797
Nat Commun. 2017 Mar 27;8:14892
pubmed: 28345670
Cancer Biol Ther. 2003 Nov-Dec;2(6):630-5
pubmed: 14688466
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Eur Thyroid J. 2020 Dec;9(Suppl 1):59-65
pubmed: 33511086
Mol Metab. 2021 Nov;53:101316
pubmed: 34400347
Cell. 2015 Jan 29;160(3):447-60
pubmed: 25619688
J Biol Chem. 2002 Jan 11;277(2):1148-57
pubmed: 11689565
Vitam Horm. 2009;80:1-31
pubmed: 19251032
Genomics. 1995 Sep 20;29(2):465-70
pubmed: 8666396
Nat Commun. 2018 Oct 24;9(1):4420
pubmed: 30356040
Oncogene. 2012 May 31;31(22):2703-14
pubmed: 21963847
Gastroenterology. 2021 Oct;161(4):1257-1269.e13
pubmed: 34175280
Protein Eng. 2001 Jan;14(1):61-5
pubmed: 11287679
Oncotarget. 2017 Apr 25;8(17):29501-29518
pubmed: 28427155
PLoS One. 2014 Aug 18;9(8):e105221
pubmed: 25133738
Endocrinology. 2003 Sep;144(9):3799-810
pubmed: 12933651
Growth Horm IGF Res. 2004 Aug;14(4):309-18
pubmed: 15231300
J Mol Biol. 2009 Dec 18;394(5):878-92
pubmed: 19835884
Commun Biol. 2019 Jun 19;2:218
pubmed: 31240256
Transgenic Res. 2011 Dec;20(6):1305-20
pubmed: 21365322
Proc Natl Acad Sci U S A. 1989 Jan;86(1):114-8
pubmed: 2911561
J Cell Biol. 2020 Jan 6;219(1):
pubmed: 31727777
Nat Commun. 2019 Oct 8;10(1):4567
pubmed: 31594955
Endocrinology. 2009 Mar;150(3):1353-60
pubmed: 18948397
FEBS Lett. 2000 Aug 11;479(1-2):15-8
pubmed: 10940380
Nat Commun. 2018 Feb 26;9(1):821
pubmed: 29483580
Biol Reprod. 2000 Jun;62(6):1593-9
pubmed: 10819760
Protein Sci. 2018 Jan;27(1):14-25
pubmed: 28710774
Nucleic Acids Res. 2004 Mar 19;32(5):1792-7
pubmed: 15034147