Structural basis for malfunction in complex II.
Complex II couples oxidoreduction of succinate and fumarate at one active site with that of quinol/quinone at a second distinct active site over 40 Å away. This process links the Krebs cycle to oxidative phosphorylation and ATP synthesis. The pathogenic mutation or inhibition of human complex II or its assembly factors is often associated with neurodegeneration or tumor formation in tissues derived from the neural crest. This brief overview of complex II correlates the clinical presentations of a large number of symptom-associated alterations in human complex II activity and assembly with the biochemical manifestations of similar alterations in the complex II homologs from Escherichia coli. These analyses provide clues to the molecular basis for diseases associated with aberrant complex II function.
Department of Pharmacology and Biochemistry, Vanderbilt University Medical Center, Nashville, Tennessee 37232. Electronic address: tina.iverson@vanderbilt.edu.
Tina M
TM
Iverson
Molecular Biology Division, Veterans Affairs Medical Center, San Francisco, California 94121; Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158.
Elena
E
Maklashina
Molecular Biology Division, Veterans Affairs Medical Center, San Francisco, California 94121; Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158. Electronic address: gary.cecchini@ucsf.edu.
Gary
G
Cecchini
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D002952:Citric Acid Cycle / Q000502:physiology*; D042963:Electron Transport Complex II / Q000502:physiology*; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D013329:Structure-Activity Relationship
D029968:Escherichia coli Proteins; D000255:Adenosine Triphosphate; D042963:Electron Transport Complex II