NDUFB2

NDUFB2 is a protein that in humans is encoded by the NDUFB2 gene. 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. 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. 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.

Structure

The NDUFB2 gene is located on the q arm of chromosome 8 in position 21.3 and spans 6,149 base pairs. The gene produces a 17.6 kDa protein composed of 159 amino acids. The NDUFB2 protein is a subunit of the enzyme NADH dehydrogenase (ubiquinone), also known as complex I, which is located in the mitochondrial inner membrane. Complex I is 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. 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.

File:NDUFB2.png

Crystal structure of Mitochondrial Respiratory Complex I.

Function

NDUFB2 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

Clinical significance

Mutations in the NDUFB2 gene are associated with mitochondrial complex I deficiency, a disorder that can cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system and the heart.

See also

• Mitochondrial diseases
• Oxidative phosphorylation
• Electron transport chain
• NADH dehydrogenase (ubiquinone)