Preferred in vivo ubiquitination sites (original) (raw)

Abstract

Motivation: 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.

Supplementary information: http://www.people.fas.harvard.edu/~catic

To whom correspondence should be addressed.

Author notes

1Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA, 2Akaza Research, Inc., 56 John F. Kennedy Street, Cambridge, MA 02138, USA and 3Lipper Center for Computational Genetics and Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA