Diversification of Quiescin sulfhydryl oxidase in a preserved framework for redox relay

BMC Evolutionary Biology

Deborah Fass²  Shifra Ben-Dor¹  Keren Limor-Waisberg² 

[1] Biological Services, Weizmann Institute of Science, Rehovot, 76100, Israel;Department of Structural Biology, Weizmann Institute of Science, Rehovot, 76100, Israel

关键词: Protein evolution;    Multi-domain;    Flavin adenine dinucleotide;    Thioredoxin;    Disulfide bond formation;   

Others  :  1129418
DOI  :  10.1186/1471-2148-13-70

 received in 2013-01-09, accepted in 2013-03-07,  发布年份 2013

【 摘 要 】

Background

The enzyme family Quiescin Sulfhydryl Oxidase (QSOX) is defined by the presence of an amino-terminal thioredoxin-fold (Trx) domain and a carboxy-terminal Erv family sulfhydryl oxidase domain. QSOX enzymes, which generate disulfide bonds and transfer them to substrate proteins, are present in a wide variety of eukaryotic species including metazoans and plants, but are absent from fungi. Plant and animal QSOXs differ in their active-site amino acid sequences and content of non-catalytic domains. The question arises, therefore, whether the Trx-Erv fusion has the same mechanistic significance in all QSOX enzymes, and whether shared features distinguish the functional domains of QSOX from other instances in which these domains occur independently. Through a study of QSOX phylogeny and an analysis of QSOX sequence diversity in light of recently determined three-dimensional structures, we sought insight into the origin and evolution of this multi-domain redox alliance.

Results

An updated collection of QSOX enzymes was used to confirm and refine the differences in domain composition and active-site sequence motif patterns of QSOXs belonging to various eukaryotic phyla. Beyond the expected phylogenetic distinction of animal and plant QSOX enzymes, trees based on individual redox-active QSOX domains show a particular distinction of the Trx domain early in plant evolution. A comparison of QSOX domains with Trx and Erv domains from outside the QSOX family revealed several sequence and structural features that clearly differentiate QSOXs from other enzymes containing either of these domains. Notably, these features, present in QSOXs of various phyla, localize to the interface between the Trx and Erv domains observed in structures of QSOX that model interdomain redox communication.

Conclusions

The infrastructure for interdomain electron relay, previously identified for animal and parasite QSOXs, is found broadly across the QSOX family, including the plant enzymes. We conclude that the conserved three-dimensional framework of the QSOX catalytic domains accommodates lineage-specific differences and paralog diversification in the amino acid residues surrounding the redox-active cysteines. Our findings indicate that QSOX enzymes are characterized not just by the presence of the two defining domain folds but also by features that promote coordinated activity.

【 授权许可】

   
2013 Limor-Waisberg et al.; licensee BioMed Central Ltd.

【 图 表 】

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