NDUFA3

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 is a protein that in humans is encoded by the NDUFA3 gene.^[3] The NDUFA3 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.^[4]

Structure

The NDUFA3 gene is located on the q arm of chromosome 19 at position 13.42, and it has a total span of 4,123 base pairs.^[3] The NDUFA3 gene produces an 11 kDa protein composed of 99 amino acids.^[5][6] NDUFA3 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.^[4] NDUFA3 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I. 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:ubiquinone oxidoreductase complex at the inner mitochondrial membrane.^[3]

Function

The human NDUFA3 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.^[3] However, NDUFA3 is an accessory subunit of the complex that is believed not to be involved in catalysis.^[7] 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.^[4]

Interactions

NDUFA3 has been shown to interact with ubiquitin C, a polyubiquitin precursor.^[3][8]

References

This article incorporates text from the United States National Library of Medicine, which is in the public domain.