The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases.
Recently, many new examples of E3 ubiquitin ligases or E3 enzymes have been found to regulate a host of cellular processes. These E3 enzymes direct the formation of multiubiquitin chains on specific protein substrates, and - typically - the subsequent destruction of those proteins. We discuss how the modular architecture of E3 enzymes connects one of two distinct classes of catalytic domains to a wide range of substrate-binding domains. In one catalytic class, a HECT domain transfers ubiquitin directly to substrate bound to a non-catalytic domain. Members of the other catalytic class, found in the SCF, VBC and APC complexes, use a RING finger domain to facilitate ubiquitylation. The separable substrate-recognition domains of E3 enzymes provides a flexible means of linking a conserved ubiquitylation function to potentially thousands of ubiquitylated substrates in eukaryotic cells.
Jackson
P K
PK
Dept of Pathology, The Stanford University School of Medicine, Stanford, CA 94305-5324, USA. pjackson@cmgm.stanford.edu
Eldridge
A G
AG
Freed
E
E
Furstenthal
L
L
Hsu
J Y
JY
Kaiser
B K
BK
Reimann
J D
JD
D000818:Animals; D020134:Catalytic Domain; D005057:Eukaryotic Cells / Q000201:enzymology; D006801:Humans; D008025:Ligases / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity / Q000502:physiology; D044767:Ubiquitin-Protein Ligases
D044767:Ubiquitin-Protein Ligases; D008025:Ligases