The NDUFB9 gene is located on the q arm of chromosome 8 in position 13.3 and is 10,884 base pairs long. The NDUFB9 protein weighs 22 kDa and is composed of 179 amino acids.[4][5] NDUFB9 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobictransmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[3] It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.[2]
Function
The protein encoded by this gene is an accessory subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I) that is not directly involved in catalysis. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein complex has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified.[2] Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[3]
Clinical significance
A mutation in NDUFB9 resulting in reduction in NDUFB9 protein and both amount and activity of complex I has been shown to be a causal mutation leading to Complex I deficiency.[6]
References
↑Gu JZ, Lin X, Wells DE (Sep 1996). "The human B22 subunit of the NADH-ubiquinone oxidoreductase maps to the region of chromosome 8 involved in branchio-oto-renal syndrome". Genomics. 35 (1): 6–10. doi:10.1006/geno.1996.0316. PMID8661098.
↑Haack, TB; Madignier, F; Herzer, M; Lamantea, E; Danhauser, K; Invernizzi, F; Koch, J; Freitag, M; Drost, R; Hillier, I; Haberberger, B; Mayr, JA; Ahting, U; Tiranti, V; Rötig, A; Iuso, A; Horvath, R; Tesarova, M; Baric, I; Uziel, G; Rolinski, B; Sperl, W; Meitinger, T; Zeviani, M; Freisinger, P; Prokisch, H (February 2012). "Mutation screening of 75 candidate genes in 152 complex I deficiency cases identifies pathogenic variants in 16 genes including NDUFB9". Journal of Medical Genetics. 49 (2): 83–9. doi:10.1136/jmedgenet-2011-100577. PMID22200994.
Further reading
Emahazion T, Beskow A, Gyllensten U, Brookes AJ (1998). "Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain". Cytogenet. Cell Genet. 82 (1–2): 115–9. doi:10.1159/000015082. PMID9763677.
Loeffen JL, Triepels RH, van den Heuvel LP, et al. (1999). "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed". Biochem. Biophys. Res. Commun. 253 (2): 415–22. doi:10.1006/bbrc.1998.9786. PMID9878551.
Lin X, Wells DE, Kimberling WJ, Kumar S (1999). "Human NDUFB9 gene: genomic organization and a possible candidate gene associated with deafness disorder mapped to chromosome 8q13". Hum. Hered. 49 (2): 75–80. doi:10.1159/000022848. PMID10077726.
Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID16169070.
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID16189514.