Composition and Structure
NADH Dehydrogenase is the largest of the respiratory complexes. In mammals, the enzyme contains 45 separate polypeptide chains. Of particular functional importance are the flavin prosthetic group (FMN) and eight iron-sulfur clusters (FeS). Of the 45 subunits, seven are encoded by the mitochondrial genome.
The structure is an "L" shape with a long membrane domain (with around 60 trans-membrane helices) and a hydrophilic peripheral domain, which includes all the known redox centres and the NADH binding site. Whereas the structure of the eukaryotic complex is not well characterised, the peripheral/hydrophilic domain of the complex from a bacterium (Thermus thermophilus) has been crystallised (PDB 2FUG).
A recent study by Roessler et al. (2010) used electron paramagnetic resonance (EPR) spectra and double electron-electron resonance (DEER) to determine the path of electron transfer through the iron-sulfur complexes, which are located in the hydrophilic domain. Seven of these clusters form a chain from the flavin to the quinone binding sites; the eighth cluster is located on the other side of the flavin, and its function is unknown. The EPR and DEER results suggest an alternating or “roller-coaster” potential energy profile for the electron transfer between the active sites and along the iron-sulfur clusters, which can optimize the rate of electron travel and allow efficient energy conversion in Complex I.
A simulational study by Hayashi and Stuchebrukhov further identified the electron tunneling pathways in atomic resolution based on the tunneling current theory. The distinct pathways between neighboring Fe/S clusters primarily consist of two cysteine ligands and one additional key residue, which was supported by sensitivity of simulated electron transfer rates to their mutations and their conservation among various complex I homologues from simple bacteria to human beings. This result shows that the crucial part of complex I developed for optimal efficiency with specific key residues during early stages of the biological evolution and has been conserved since then. Internal water between protein subunits was identified as an essential mediator enhancing the overall electron transfer rate to achieve physiologically significant value.
Read more about this topic: NADH Dehydrogenase
Famous quotes containing the words composition and, composition and/or structure:
“The naive notion that a mother naturally acquires the complex skills of childrearing simply because she has given birth now seems as absurd to me as enrolling in a nine-month class in composition and imagining that at the end of the course you are now prepared to begin writing War and Peace.”
—Mary Kay Blakely (20th century)
“Since body and soul are radically different from one another and belong to different worlds, the destruction of the body cannot mean the destruction of the soul, any more than a musical composition can be destroyed when the instrument is destroyed.”
—Oscar Cullman. Immortality of the Soul or Resurrection of the Dead? The Witness of the New Testament, ch. 1, Epworth Press (1958)
“Women over fifty already form one of the largest groups in the population structure of the western world. As long as they like themselves, they will not be an oppressed minority. In order to like themselves they must reject trivialization by others of who and what they are. A grown woman should not have to masquerade as a girl in order to remain in the land of the living.”
—Germaine Greer (b. 1939)