Clamping, bending, and twisting inter-domain motions in the misfold-recognizing portion of UDP-glucose: Glycoprotein glucosyltransferase.
GT24 domain
Parodi limit
UGGT
X-ray diffraction
glycoprotein folding
misfold sensing
misfolding
molecular dynamics
negative-stain EM
re-glucosylation
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
received:
05
03
2020
revised:
07
09
2020
accepted:
24
11
2020
pubmed:
23
12
2020
medline:
24
11
2021
entrez:
22
12
2020
Statut:
ppublish
Résumé
UDP-glucose:glycoprotein glucosyltransferase (UGGT) flags misfolded glycoproteins for ER retention. We report crystal structures of full-length Chaetomium thermophilum UGGT (CtUGGT), two CtUGGT double-cysteine mutants, and its TRXL2 domain truncation (CtUGGT-ΔTRXL2). CtUGGT molecular dynamics (MD) simulations capture extended conformations and reveal clamping, bending, and twisting inter-domain movements. We name "Parodi limit" the maximum distance on the same glycoprotein between a site of misfolding and an N-linked glycan that can be reglucosylated by monomeric UGGT in vitro, in response to recognition of misfold at that site. Based on the MD simulations, we estimate the Parodi limit as around 70-80 Å. Frequency distributions of distances between glycoprotein residues and their closest N-linked glycosylation sites in glycoprotein crystal structures suggests relevance of the Parodi limit to UGGT activity in vivo. Our data support a "one-size-fits-all adjustable spanner" UGGT substrate recognition model, with an essential role for the UGGT TRXL2 domain.
Identifiants
pubmed: 33352114
pii: S0969-2126(20)30464-0
doi: 10.1016/j.str.2020.11.017
pmc: PMC8024514
pii:
doi:
Substances chimiques
Fungal Proteins
0
Glycoproteins
0
Glucosyltransferases
EC 2.4.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
357-370.e9Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Free Radic Biol Med. 2017 Jul;108:383-393
pubmed: 28363604
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Methods Mol Biol. 2008;426:145-59
pubmed: 18542861
Acta Crystallogr D Biol Crystallogr. 2005 Oct;61(Pt 10):1426-31
pubmed: 16204897
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
Acta Crystallogr F Struct Biol Commun. 2015 Jul;71(Pt 7):831-7
pubmed: 26144227
Adv Exp Med Biol. 2018;1104:149-169
pubmed: 30484248
Proteins. 2018 Mar;86 Suppl 1:27-50
pubmed: 28960539
Biochem Biophys Res Commun. 2015 Jun 19;462(1):58-63
pubmed: 25935482
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):22-5
pubmed: 20057045
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):404-17
pubmed: 22505260
Nat Biotechnol. 2012 Oct;30(10):918-20
pubmed: 23051804
J Oncol. 2019 Oct 1;2019:8384913
pubmed: 31662755
FEBS J. 2020 Oct;287(20):4322-4340
pubmed: 32285592
Acta Crystallogr D Biol Crystallogr. 2006 Oct;62(Pt 10):1243-50
pubmed: 17001101
Proteomics. 2009 Mar;9(6):1548-55
pubmed: 19235167
Biochim Biophys Acta Gen Subj. 2020 Dec;1864(12):129709
pubmed: 32858085
Sci Rep. 2017 Sep 22;7(1):12142
pubmed: 28939828
J Mol Biol. 2009 Mar 27;387(2):335-47
pubmed: 19356590
J Chem Theory Comput. 2015 Aug 11;11(8):3696-713
pubmed: 26574453
EMBO J. 2005 May 4;24(9):1730-8
pubmed: 15861139
Angew Chem Int Ed Engl. 2016 Mar 14;55(12):3968-71
pubmed: 26890995
Org Biomol Chem. 2016 Jul 7;14(25):6088-94
pubmed: 27248046
Proc Natl Acad Sci U S A. 2016 Aug 9;113(32):E4630-8
pubmed: 27462106
J Biol Chem. 2005 May 6;280(18):18138-41
pubmed: 15746090
Glycobiology. 2016 Sep;26(9):999-1006
pubmed: 27496766
Biochemistry. 1989 Oct 3;28(20):8108-16
pubmed: 2532539
Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):86-91
pubmed: 12518055
J Chem Theory Comput. 2013 Jul 9;9(7):3084-95
pubmed: 26583988
J Biol Chem. 1999 May 14;274(20):14094-9
pubmed: 10318825
J Biol Chem. 2006 Oct 20;281(42):31502-8
pubmed: 16940048
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Biochemistry. 2009 Apr 7;48(13):2933-40
pubmed: 19222173
Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):8544-8549
pubmed: 28739903
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2210-21
pubmed: 15572774
J Am Chem Soc. 2018 Dec 19;140(50):17499-17507
pubmed: 30475607
Protein Sci. 2018 Jan;27(1):135-145
pubmed: 28884485
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):368-80
pubmed: 22505257
Biochem Biophys Res Commun. 2014 Aug 29;451(3):356-60
pubmed: 25094044
J Mol Graph Model. 2009 Sep;28(2):131-9
pubmed: 19473861
J Biol Chem. 2017 Jul 7;292(27):11499-11507
pubmed: 28490633
Trends Cell Biol. 1992 May;2(5):145-9
pubmed: 14731969
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):293-302
pubmed: 21460447
Nat Struct Biol. 2000 Apr;7(4):278-80
pubmed: 10742170
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14
pubmed: 23793146
Biochemistry. 2008 Sep 9;47(36):9416-27
pubmed: 18702531
Nucleic Acids Res. 2015 Jul 1;43(W1):W314-9
pubmed: 25908787
PLoS One. 2012;7(8):e42998
pubmed: 22905195
Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4956-61
pubmed: 21383159
Biochem Mol Biol Educ. 2016 Sep 10;44(5):433-7
pubmed: 27241834
Nat Struct Mol Biol. 2004 Feb;11(2):128-34
pubmed: 14730348
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
J Appl Crystallogr. 2009 Dec 1;42(Pt 6):1035-1042
pubmed: 22477774
Mol Biol Cell. 2002 Dec;13(12):4456-69
pubmed: 12475965
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4
pubmed: 24753421
Mol Syst Biol. 2017 Jul 25;13(7):936
pubmed: 28743795