Structural highlights
Disease
[ADCK3_HUMAN] Autosomal recessive ataxia due to ubiquinone deficiency. The disease is caused by mutations affecting the gene represented in this entry.
Function
[ADCK3_HUMAN] Putative protein kinase involved in the biosynthesis of coenzyme Q since it is able to rescue partially coenzyme Q6 biosynthesis of yeast COQ8 mutants. May be a chaperone-like protein essential for the proper conformation and functioning of protein complexes in the respiratory chain.[1]
Publication Abstract from PubMed
The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for unknown reasons. Here, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flips this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.
Mitochondrial ADCK3 Employs an Atypical Protein Kinase-like Fold to Enable Coenzyme Q Biosynthesis.,Stefely JA, Reidenbach AG, Ulbrich A, Oruganty K, Floyd BJ, Jochem A, Saunders JM, Johnson IE, Minogue CE, Wrobel RL, Barber GE, Lee D, Li S, Kannan N, Coon JJ, Bingman CA, Pagliarini DJ Mol Cell. 2015 Jan 8;57(1):83-94. doi: 10.1016/j.molcel.2014.11.002. Epub 2014, Dec 11. PMID:25498144[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Xie LX, Hsieh EJ, Watanabe S, Allan CM, Chen JY, Tran UC, Clarke CF. Expression of the human atypical kinase ADCK3 rescues coenzyme Q biosynthesis and phosphorylation of Coq polypeptides in yeast coq8 mutants. Biochim Biophys Acta. 2011 May;1811(5):348-60. doi: 10.1016/j.bbalip.2011.01.009., Epub 2011 Feb 4. PMID:21296186 doi:http://dx.doi.org/10.1016/j.bbalip.2011.01.009
- ↑ Stefely JA, Reidenbach AG, Ulbrich A, Oruganty K, Floyd BJ, Jochem A, Saunders JM, Johnson IE, Minogue CE, Wrobel RL, Barber GE, Lee D, Li S, Kannan N, Coon JJ, Bingman CA, Pagliarini DJ. Mitochondrial ADCK3 Employs an Atypical Protein Kinase-like Fold to Enable Coenzyme Q Biosynthesis. Mol Cell. 2015 Jan 8;57(1):83-94. doi: 10.1016/j.molcel.2014.11.002. Epub 2014, Dec 11. PMID:25498144 doi:http://dx.doi.org/10.1016/j.molcel.2014.11.002
