Preferred in vivo ubiquitination sites.
BACKGROUND
The conjugation of ubiquitin to target molecules involves several enzymatic steps. Little is known about the specificity of ubiquitination. How E3 ligases select their substrate and which lysines are targeted for ubiquitin conjugation is largely an enigma. The object of this study is to identify preferred ubiquitination sites. Genetic approaches to study this question have proven difficult, because of the redundancy of ligases and the lack of strictly required motifs. However, a better understanding of acceptor site selection could help to predict ubiquitination sites and clarify yet unsolved structure-function relationships of the transfer reaction.


RESULTS
In an effort to define preferences for ubiquitination, we systematically analyzed structure and sequence of 135 known ubiquitination sites in 95 proteins in Saccharomyces cerevisiae. The results show clear structural preferences for ubiquitin ligation to target proteins, and compartment-specific amino acid patterns in close proximity to the modified side chain.


BACKGROUND
http://www.people.fas.harvard.edu/~catic.
Catic
André
A
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Catic@fas.harvard.edu <Catic@fas.harvard.edu>
Collins
Cal
C
Church
George M
GM
Ploegh
Hidde L
HL
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D004789:Enzyme Activation; D008968:Molecular Conformation; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000737:chemistry*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D025801:Ubiquitin / Q000032:analysis / Q000737:chemistry*; D044764:Ubiquitin-Activating Enzymes / Q000032:analysis / Q000737:chemistry*
D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D044764:Ubiquitin-Activating Enzymes