4p22

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Crystal Structure of N-terminal Fragments of E1

Structural highlights

4p22 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[UBA1_HUMAN] X-linked distal arthrogryposis multiplex congenita. The disease is caused by mutations affecting the gene represented in this entry.

Function

[UBA1_HUMAN] Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system. Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites.^[1]

Publication Abstract from PubMed

Ubiquitin-activating enzyme (E1) is a key regulator in protein ubiquitination, which lies on the upstream of the ubiquitin-related pathways and determines the activation of the downstream enzyme cascade. Thus far, no structural information about the human ubiquitin-activating enzyme has been reported. We expressed and purified the N-terminal domains of human E1 and determined their crystal structures, which contain inactive adenylation domain (IAD) and the first catalytic cysteine half-domain (FCCH). This study presents the crystal structure of human E1 fragment for the first time. The main structure of both IAD and FCCH superimposed well with their corresponding domains in yeast Uba1, but their relative positions vary significantly. This work provides new structural insights in understanding the mechanisms of ubiquitin activation in humans.

Expression, purification, and crystal structure of N-terminal domains of human ubiquitin-activating enzyme (E1).,Xie ST Biosci Biotechnol Biochem. 2014;78(9):1542-9. doi: 10.1080/09168451.2014.923301. , Epub 2014 Jun 9. PMID:25209502^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Moudry P, Lukas C, Macurek L, Hanzlikova H, Hodny Z, Lukas J, Bartek J. Ubiquitin-activating enzyme UBA1 is required for cellular response to DNA damage. Cell Cycle. 2012 Apr 15;11(8):1573-82. doi: 10.4161/cc.19978. Epub 2012 Apr 15. PMID:22456334 doi:http://dx.doi.org/10.4161/cc.19978
↑ Xie ST. Expression, purification, and crystal structure of N-terminal domains of human ubiquitin-activating enzyme (E1). Biosci Biotechnol Biochem. 2014;78(9):1542-9. doi: 10.1080/09168451.2014.923301. , Epub 2014 Jun 9. PMID:25209502 doi:http://dx.doi.org/10.1080/09168451.2014.923301