tailieunhanh - Báo cáo sinh học: "Mechanisms of ubiquitin transfer by the anaphase-promoting complex"

Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: Mechanisms of ubiquitin transfer by the anaphase-promoting complex. | Journal of Biology Review Mechanisms of ubiquitin transfer by the anaphase-promoting complex Mary E Matyskiela Monica C Rodrigo-Brenni and David O Morgan Address Departments of Physiology and Biochemistry and Biophysics University of California San Francisco CA 94158 USA. Correspondence David O Morgan. Email Abstract The anaphase-promoting complex APC is a ubiquitin-protein ligase required for the completion of mitosis in all eukaryotes. Recent mechanistic studies reveal how this remarkable enzyme combines specificity in substrate binding with flexibility in ubiquitin transfer thereby allowing the modification of multiple lysines on the substrate as well as specific lysines on ubiquitin itself. In addition the APC and or its substrates must be flexible enough to allow the transfer of ubiquitin to multiple lysines on the target protein and to specific lysines on ubiquitin itself Figure 2a . We will describe the basis for this balance of specificity and flexibility by focusing on two key issues substrate binding and the catalysis of ubiquitin transfer. These features of APC mechanism are likely to have important implications for ubiquitin-protein ligases in general. The function of a ubiquitin-protein ligase as its name implies is to catalyze the ligation of the small protein ubiquitin to other proteins. Ubiquitin attachment occurs primarily at lysine residues and in many cases the reaction is repeated at several lysines on the same protein and on ubiquitin itself resulting in decoration of the target protein with multiple polyubiquitin chains which send the protein to the proteasome for destruction or alter other aspects of protein function 1 2 . Protein ubiquitination is a versatile and effective mechanism for controlling protein behavior and has been adapted for diverse purposes by many regulatory systems in the eukaryotic cell. There is enormous complexity in the mechanisms that allow ubiquitin-protein ligases to recognize and repeatedly .