The UBR-box and its relationship to binuclear RING-like treble clef zinc fingers

Biology Direct

Gurmeet Kaur¹  Srikrishna Subramanian¹ 

[1] CSIR-Institute of Microbial Technology (IMTECH), Sector 39-A, Chandigarh 160036, India

关键词: U-box;    novel fold;    N-end rule;    ZZ domain;    B-box;    zinc fingers;    Binuclear treble clefs;   

Others  :  1227866
DOI  :  10.1186/s13062-015-0066-5

 received in 2015-03-09, accepted in 2015-07-02,  发布年份 2015

【 摘 要 】

Background

The N-end rule pathway is a part of the ubiquitin–dependent proteolytic system wherein N-recognin proteins recognize the amino terminal degradation signals (N-degrons) of the substrate. The type 1 N-degron recognizing UBR-box domain of the eukaryotic Arg/N-end rule pathway is known to possess a novel three-zinc-stabilized heart-shaped fold.

Results

Using sequence and structure analysis we argue that the UBR-box fold emerged from a binuclear RING-like treble clef zinc finger. The RING-like core is preserved in the UBR-box and the metal-chelating motifs display significant sequence and structural similarity to B-box and ZZ domains. UBR-box domains retrieved in our analysis co-occur with a variety of other protein domains, suggestive of its involvement in diverse biological roles. The UBR-box is a unique family of RING-like treble clefs as it displays a distinct circular permutation at the zinc-knuckle of the first zinc-binding site unlike other documented permutations of the RING-like domains which occur at the second zinc-binding site. The circular permutation of the RING-like treble clef scaffold has possibly aided the gain of a novel and relatively deep cleft suited for binding N-degrons. The N- and C-terminal extensions to the circularly permuted RING-like region bind a third zinc ion, which likely provides additional stability to the domain by keeping the two halves of the permuted zinc-knuckle together.

Conclusions

Structural modifications and extensions to the RING-like core have resulted in a novel UBR-box fold, which can recognize and target the type 1 N-degron containing proteins for ubiquitin-mediated proteolysis. The UBR-box appears to have emerged during the expansion of ubiquitin system pathway-related functions in eukaryotes, but is also likely to have other non-N-recognin functions as well.

Reviewers

This article was reviewed by Eugene Koonin, Balaji Santhanam, Kira S. Makarova.

【 授权许可】

   
2015 Kaur and Subramanian.

【 图 表 】

Fig. 1.

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Fig. 3.

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