TY - JOUR
T1 - Tetrameric Assembly of Monoubiquitin Accurately Mimics the Lys11 Polyubiquitin Chain Structure
AU - Levin-Kravets, Olga
AU - Shohat, Noa
AU - Prag, Gali
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2015/8/4
Y1 - 2015/8/4
N2 - Specific lysine residues on the ubiquitin surface were selected during the course of evolution to form different polyubiquitin chain structures that signal diverse cellular processes. A vast number of ubiquitin receptors specifically recognize and decode the signals conferred by these polyubiquitin chains. The mechanisms of formation and the structure of Lys11-linked ubiquitin, which signals for cell-cycle and innate immune control, have been elucidated. Here, we present a new crystal structure of monomeric ubiquitin that accurately mimics one of the structures of Lys11-linked ubiquitin. Analysis of the ubiquitin:ubiquitin interface demonstrates structural fitness and specificity. The interaction is exclusively hydrophilic, leaving the Ile44 hydrophobic patch, a major recognition site for ubiquitin receptors, exposed. These noncovalent ubiquitin:ubiquitin interactions are nearly identical to those reported for Lys11-linked ubiquitin and seem to play a significant role in stabilizing the crystal structure without the isopeptide bond. In vitro cross-linking analysis with wild-type ubiquitin or its mutants partially mimics the interactions in the crystal. We suggest that these interactions may play a biological role in transmitting Lys11-linked ubiquitin chain-type cellular signals.
AB - Specific lysine residues on the ubiquitin surface were selected during the course of evolution to form different polyubiquitin chain structures that signal diverse cellular processes. A vast number of ubiquitin receptors specifically recognize and decode the signals conferred by these polyubiquitin chains. The mechanisms of formation and the structure of Lys11-linked ubiquitin, which signals for cell-cycle and innate immune control, have been elucidated. Here, we present a new crystal structure of monomeric ubiquitin that accurately mimics one of the structures of Lys11-linked ubiquitin. Analysis of the ubiquitin:ubiquitin interface demonstrates structural fitness and specificity. The interaction is exclusively hydrophilic, leaving the Ile44 hydrophobic patch, a major recognition site for ubiquitin receptors, exposed. These noncovalent ubiquitin:ubiquitin interactions are nearly identical to those reported for Lys11-linked ubiquitin and seem to play a significant role in stabilizing the crystal structure without the isopeptide bond. In vitro cross-linking analysis with wild-type ubiquitin or its mutants partially mimics the interactions in the crystal. We suggest that these interactions may play a biological role in transmitting Lys11-linked ubiquitin chain-type cellular signals.
UR - http://www.scopus.com/inward/record.url?scp=84938632468&partnerID=8YFLogxK
U2 - 10.1021/acs.biochem.5b00498
DO - 10.1021/acs.biochem.5b00498
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AN - SCOPUS:84938632468
SN - 0006-2960
VL - 54
SP - 4704
EP - 4710
JO - Biochemistry
JF - Biochemistry
IS - 30
ER -