Structure-function relationship in UCP1. Int J Obes Relat Metab Disord 1999 Jun;23 Suppl 6:S24-9
Date
08/24/1999Pubmed ID
10454117DOI
10.1038/sj.ijo.0800939Scopus ID
2-s2.0-0032995203 (requires institutional sign-in at Scopus site) 69 CitationsAbstract
The function of uncoupling protein (UCP1) as a H+ transporter regulated by nucleotide binding is elucidated. H+ transport requires fatty acids (FA) with relatively wide structural tolerance. The nucleotide binding site is specific for purine nucleotides and tolerates a number of derivatives. The strong pH dependency facilitates regulation of nucleotide binding and thus H+ translocation. The structure-function relationship of UCP1 has been analysed by various probes and by mutagenesis. According to our model, FA are a cofactor in H+ transport, providing H+ shuttling carboxyl groups in the translocation channel. By mutagenesis, additional H+ translocating groups at both sides of the translocation channel were found. Two pH sensors, controlling nucleotide binding, were identified in accordance with earlier postulates deduced from the pH dependence of nucleoside diphosphate (NDP) and nucleoside triphosphate (NTP). A common pH sensor E190 and a specific pH sensor H214 for triphosphates only, control access to the phosphate binding moiety. The three mitochondrial carrier family characteristic intrahelical arginines are essential for nucleotide binding. Mutagenesis of other charged residues reveals their role in structure stabilisation and/or has more generalised effects due to charge relay networks in UCP1.
Author List
Klingenberg M, Echtay KS, Bienengraeber M, Winkler E, Huang SGMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Carrier Proteins
Humans
Hydrogen
Ion Channels
Membrane Proteins
Mitochondrial Proteins
Molecular Sequence Data
Mutagenesis, Site-Directed
Nucleotides
Protein Structure, Secondary
Structure-Activity Relationship
Uncoupling Protein 1
