Retinal degeneration 3 (RD3) protein, a retinal guanylyl cyclase regulator, forms a monomeric and elongated four-helix bundle.
guanylate cyclase (guanylyl cyclase)
nuclear magnetic resonance (NMR)
photoreceptor
phototransduction
retinal degeneration
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:
15 02 2019
15 02 2019
Historique:
received:
02
10
2018
revised:
07
12
2018
pubmed:
19
12
2018
medline:
30
4
2019
entrez:
19
12
2018
Statut:
ppublish
Résumé
Retinal degeneration 3 (RD3) protein promotes accumulation of retinal membrane guanylyl cyclase (RetGC) in the photoreceptor outer segment and suppresses RetGC activation by guanylyl cyclase-activating proteins (GCAPs). Mutations truncating RD3 cause severe congenital blindness by preventing the inhibitory binding of RD3 to the cyclase. The high propensity of RD3 to aggregate in solution has prevented structural analysis. Here, we produced a highly soluble variant of human RD3 (residues 18-160) that is monomeric and can still bind and negatively regulate RetGC. The NMR solution structure of RD3 revealed an elongated backbone structure (70 Å long and 30 Å wide) consisting of a four-helix bundle with a long unstructured loop between helices 1 and 2. The structure reveals that RD3 residues previously implicated in the RetGC binding map to a localized and contiguous area on the structure, involving a loop between helices 2 and 3 and adjacent parts of helices 3 and 4. The NMR structure of RD3 was validated by mutagenesis. Introducing Trp
Identifiants
pubmed: 30559291
pii: S0021-9258(20)39987-7
doi: 10.1074/jbc.RA118.006106
pmc: PMC6378972
doi:
Substances chimiques
Eye Proteins
0
RD3 protein, human
0
Receptors, Cell Surface
0
guanylate cyclase 1
0
Guanylate Cyclase
EC 4.6.1.2
Banques de données
PDB
['6DRF']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2318-2328Subventions
Organisme : NEI NIH HHS
ID : R01 EY011522
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY012347
Pays : United States
Informations de copyright
© 2019 Peshenko et al.
Références
Invest Ophthalmol Vis Sci. 2012 Jun 08;53(7):3463-72
pubmed: 22531706
J Biomol NMR. 1995 Nov;6(3):277-93
pubmed: 8520220
Biomacromolecules. 2003 Nov-Dec;4(6):1727-32
pubmed: 14606902
Subcell Biochem. 2007;45:71-91
pubmed: 18193635
Biomol NMR Assign. 2018 Apr;12(1):167-170
pubmed: 29327102
Biochemistry. 2011 Nov 8;50(44):9511-9
pubmed: 21928830
Neuron. 1994 Jun;12(6):1345-52
pubmed: 7912093
J Biol Chem. 2004 Apr 23;279(17):16903-6
pubmed: 14993224
Hum Mol Genet. 2013 Jan 1;22(1):168-83
pubmed: 23035049
J Biol Chem. 2015 Feb 6;290(6):3488-99
pubmed: 25477517
Mol Cell Biochem. 2010 Jan;334(1-2):117-24
pubmed: 19953307
J Biol Chem. 1991 May 5;266(13):8634-7
pubmed: 1673683
J Biol Chem. 2001 Jul 13;276(28):26218-29
pubmed: 11306565
J Biomol NMR. 2009 Aug;44(4):213-23
pubmed: 19548092
J Biol Chem. 2015 Aug 7;290(32):19584-96
pubmed: 26100624
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
J Biomol NMR. 1998 Feb;11(2):135-52
pubmed: 9679292
Biochemistry. 2010 Feb 23;49(7):1469-76
pubmed: 20088570
Hum Mol Genet. 2013 Oct 1;22(19):3894-905
pubmed: 23740938
Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5535-9
pubmed: 7777544
Proc Natl Acad Sci U S A. 1998 May 26;95(11):5993-7
pubmed: 9600905
Biochemistry. 1994 Sep 6;33(35):10743-53
pubmed: 8075075
Curr Opin Chem Biol. 1998 Oct;2(5):564-70
pubmed: 9818180
Curr Protoc Cell Biol. 2008 Jun;Chapter 4:Unit 4.19
pubmed: 18551422
Cell Logist. 2014 Jun 04;4:e29390
pubmed: 25279249
Front Mol Neurosci. 2015 Nov 17;8:67
pubmed: 26635520
Gene. 1989 Apr 15;77(1):61-8
pubmed: 2744488
J Biol Chem. 2008 Aug 1;283(31):21747-57
pubmed: 18541533
Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):602-6
pubmed: 7831337
J Biomol NMR. 1996 Dec;8(4):477-86
pubmed: 9008363
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13414-9
pubmed: 9391039
J Magn Reson. 1998 Oct;134(2):365-9
pubmed: 9761712
J Biol Chem. 2015 Mar 13;290(11):6913-24
pubmed: 25616661
Science. 1997 Nov 7;278(5340):1111-4
pubmed: 9353189
Nat Protoc. 2008;3(4):679-90
pubmed: 18388951
J Biomol NMR. 2016 Jun;65(2):51-7
pubmed: 27169728
Front Mol Neurosci. 2014 May 26;7:44
pubmed: 24904271
Am J Ophthalmol. 2007 Dec;144(6):791-811
pubmed: 17964524
J Biol Chem. 2007 Mar 23;282(12):8837-47
pubmed: 17255100
J Biol Chem. 2016 Sep 9;291(37):19713-23
pubmed: 27471269
Am J Hum Genet. 2006 Dec;79(6):1059-70
pubmed: 17186464
Methods Cell Biol. 1989;30:127-56
pubmed: 2538708
J Biol Chem. 2006 Aug 18;281(33):23830-41
pubmed: 16793776
Prog Retin Eye Res. 2018 Mar;63:69-91
pubmed: 29061346
J Magn Reson. 2003 Jan;160(1):65-73
pubmed: 12565051
Biochem Soc Trans. 1991 Apr;19(2):485
pubmed: 1889645
Annu Rev Physiol. 2002;64:153-87
pubmed: 11826267
Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21158-63
pubmed: 21078983
Front Mol Neurosci. 2014 Mar 17;7:19
pubmed: 24672427
Front Mol Neurosci. 2018 Feb 21;11:52
pubmed: 29515371