Structure and function of mitochondrial carriers - role of the transmembrane helix P and G residues in the gating and transport mechanism.
To date, 22 mitochondrial carrier subfamilies have been functionally identified based on substrate specificity. Structural, functional and bioinformatics studies have pointed to the existence in the mitochondrial carrier superfamily of a substrate-binding site in the internal carrier cavity, of two salt-bridge networks or gates that close the cavity alternatively on the matrix or the cytosolic side of the membrane, and of conserved prolines and glycines in the transmembrane alpha-helices. The significance of these properties in the structural changes occurring during the catalytic substrate translocation cycle are discussed within the context of a transport mechanism model. Most experimentally produced and disease-causing missense mutations concern carrier regions corresponding to the substrate-binding site, the two gates and the conserved prolines and glycines.
Palmieri
Ferdinando
F
Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, Bari, Italy. fpalm@farmbiol.uniba.it
Pierri
Ciro Leonardo
CL
D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D028361:Mitochondrial Diseases / Q000209:etiology; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D024101:Mitochondrial Proteins