@article{Kelsall:2021:10.1101/2021.09.10.459791,
author = {Kelsall, IR and McCrory, EH and Xu, Y and Scudamore, CL and Nanda, SK and Mancebo-Gamella, P and Wood, NT and Knebel, A and Matthews, SJ and Cohen, P},
doi = {10.1101/2021.09.10.459791},
title = {HOIL-1-catalysed ubiquitylation of unbranched glucosaccharides and its activation by ubiquitin oligomers},
url = {http://dx.doi.org/10.1101/2021.09.10.459791},
year = {2021}
}

Download

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>HOIL-1, a component of the Linear Ubiquitin Assembly Complex (LUBAC), ubiquitylates serine and threonine residues in proteins, forming ester bonds (Kelsall et al, 2019, PNAS 116, 13293-13298). Here we report that mice expressing the E3 ligase-inactive HOIL-1[C458S] mutant accumulate polyglucosan in brain, cardiac muscle and other organs, indicating that HOIL-1’s E3 ligase activity is essential to prevent these toxic polysaccharide deposits from accumulating. We found that HOIL-1 monoubiquitylates glycogen and α1:4-linked maltoheptaose <jats:italic>in vitro</jats:italic> and identify the C6 hydroxyl moiety of glucose as the site of ester-linked ubiquitylation. The HOIL-1-catalysed monoubiquitylation of maltoheptaose was accelerated >100-fold by Met1-linked or Lys63-linked ubiquitin oligomers, which interact with the catalytic RBR domain of HOIL-1. HOIL-1 also transferred preformed ubiquitin oligomers to maltoheptaose <jats:italic>en bloc</jats:italic>, producing polyubiquitylated maltoheptaose in one catalytic step. The Sharpin and HOIP components of LUBAC, but not HOIL-1, bound to amylose resin <jats:italic>in vitro</jats:italic>, suggesting a potential function in targeting HOIL-1 to unbranched glucosaccharides in cells. We suggest that monoubiquitylation of unbranched glucosaccharides may initiate their removal by glycophagy to prevent precipitation as polyglucosan.</jats:p>
AU  - Kelsall,IR
AU  - McCrory,EH
AU  - Xu,Y
AU  - Scudamore,CL
AU  - Nanda,SK
AU  - Mancebo-Gamella,P
AU  - Wood,NT
AU  - Knebel,A
AU  - Matthews,SJ
AU  - Cohen,P
DO  - 10.1101/2021.09.10.459791
PY  - 2021///
TI  - HOIL-1-catalysed ubiquitylation of unbranched glucosaccharides and its activation by ubiquitin oligomers
UR  - http://dx.doi.org/10.1101/2021.09.10.459791
ER  - 

Download