期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 431, 期 3, 页码 463-478出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2018.10.007
关键词
UFM1; UBA5; ubiquitin-like proteins; E1 activating enzymes; crystal structure
资金
- Marie Curie Career Integration Grant [PCIG13-GA-2013-630755]
- Israel Science Foundation [1383/17]
- Israeli Cancer Association [20180069]
Modification of proteins by the ubiquitin-like protein, UFM1, requires activation of UFM1 by the E1 activating enzyme, UBA5. In humans, UBA5 possesses two isoforms, each comprising an adenylation domain, but only one containing an N-terminal extension. Currently, the role of the N-terminal extension in UFM1 activation is not clear. Here we provide structural and biochemical data on UBA5 N-terminal extension to understand its contribution to UFM1 activation. The crystal structures of the UBA5 long isoform bound to ATP with and without UFM1 show that the N-terminus not only is directly involved in ATP binding but also affects how the adenylation domain interacts with ATP. Surprisingly, in the presence of the N-terminus, UBA5 no longer retains the 1:2 ratio of ATP to UBA5, but rather this becomes a 1:1 ratio. Accordingly, the N-terminus significantly increases the affinity of ATP to UBA5. Finally, the N-terminus, although not directly involved in the E2 binding, stimulates transfer of UFM1 from UBA5 to the E2, UFC1. 2018 Elsevier Ltd. All rights reserved.
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