IndraLab

Statements



sparser
"On the molecular level, we find binding of OTULIN to linear ubiquitin to be compromised by both variants; however, protein stability and catalytic activity is most affected by OTULIN variant p."

sparser
"Using our OTULIN ABP we demonstrate that OTULIN is constitutively active in cells, and that substrate-bound OTULIN associates with the linear ubiquitin chain assembly complex (LUBAC)."

sparser
"Disease-associated mutations reside in the OTU domain and are predicted to affect binding of OTULIN to linear Ub chains."

sparser
"The interaction between Y91 and M86, which is lost in the mutant M86I, might, thus, also play a role in binding of OTULIN to linear ubiquitin (Fig  xref )."

sparser
"It is likely, therefore, that the W167S replacement affects the orientation of the helical arm's S1 site, made up of L259, A262, and R263 toward the I44 patch of distal ubiquitin, thereby indirectly interfering with OTULIN’s binding (K M ) to linear ubiquitin (Fig  xref )."

sparser
"In‐depth biochemical analysis revealed how both OTULIN variants contribute to diminished OTULIN protein expression and defective hydrolysis of linear ubiquitin linkages observed in patient‐derived cells: whereas binding of OTULIN to linear ubiquitin was compromised by both variants, protein stability and catalytic activity was most affected by the OTULIN variant p."

sparser
"Pull-downs demonstrate that substrate-bound OTULIN associates with the linear ubiquitin chain assembly complex (LUBAC)."

sparser
"In summary, we find binding of OTULIN to linear ubiquitin to be compromised by both variants; however, protein stability and catalytic activity is most affected by the OTULIN variant p."

sparser
"Leu272 is located in a helix of the catalytic OTU domain that forms part of the binding pocket for M1-linked diUb, and mutation to Pro would be predicted to disrupt OTULIN Ub binding ( xref F)."

sparser
"Collectively, this structural analysis suggests that both substitutions, M86I and W167S, may interfere with binding of OTULIN to linear ubiquitin (Fig  xref )."

sparser
"OTULIN variants compromise binding of OTULIN to linear ubiquitin and differentially affect OTULIN’s intrinsic stability and catalytic activity."