Molecular modelling of prohibitin domains
Author(s)
Winter, Anja
Kamarainen, Outi
Hofmann, Andreas
Year published
2007
Metadata
Show full item recordAbstract
Prohibitins comprise a family of highly conserved ubiquitous eukaryotic proteins that mainly localize to the mitochondria. They have been implicated in important cellular processes such as cellular signaling and transcriptional control, apoptosis, cellular senescence, and mitochondrial biogenesis. Using molecular modeling techniques, we have generated structural models of human prohibitions BAP32 and BAP37 which have previously been shown to exist as large ring-like oligomers in the membrane-bound state. The middle domain of prohibitins is evolutionary conserved in the family of SPFH (PHB) domain proteins. Based on the known ...
View more >Prohibitins comprise a family of highly conserved ubiquitous eukaryotic proteins that mainly localize to the mitochondria. They have been implicated in important cellular processes such as cellular signaling and transcriptional control, apoptosis, cellular senescence, and mitochondrial biogenesis. Using molecular modeling techniques, we have generated structural models of human prohibitions BAP32 and BAP37 which have previously been shown to exist as large ring-like oligomers in the membrane-bound state. The middle domain of prohibitins is evolutionary conserved in the family of SPFH (PHB) domain proteins. Based on the known structure of flotillin-2, another member of the SPFH domain family, we have generated homology models for BAP32 and BAP37, and elucidated the implications for formation of high molecular weight oligomers. A model for the dimeric building block of BAP32:BAP37 for such assemblies was generated and its stability scrutinized by molecular dynamics simulations. The model of BAP32 was also analyzed as to potential ligand binding sites and the previously identified ligand melanogenin was docked into a membrane-proximal cavity. The results are discussed in the context of prohibitin interactions with mitochondrial AAA-proteases and we suggest two possible interaction interfaces between the BAP32:BAP37 building block and the protease.
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View more >Prohibitins comprise a family of highly conserved ubiquitous eukaryotic proteins that mainly localize to the mitochondria. They have been implicated in important cellular processes such as cellular signaling and transcriptional control, apoptosis, cellular senescence, and mitochondrial biogenesis. Using molecular modeling techniques, we have generated structural models of human prohibitions BAP32 and BAP37 which have previously been shown to exist as large ring-like oligomers in the membrane-bound state. The middle domain of prohibitins is evolutionary conserved in the family of SPFH (PHB) domain proteins. Based on the known structure of flotillin-2, another member of the SPFH domain family, we have generated homology models for BAP32 and BAP37, and elucidated the implications for formation of high molecular weight oligomers. A model for the dimeric building block of BAP32:BAP37 for such assemblies was generated and its stability scrutinized by molecular dynamics simulations. The model of BAP32 was also analyzed as to potential ligand binding sites and the previously identified ligand melanogenin was docked into a membrane-proximal cavity. The results are discussed in the context of prohibitin interactions with mitochondrial AAA-proteases and we suggest two possible interaction interfaces between the BAP32:BAP37 building block and the protease.
View less >
Journal Title
Proteins: Structure, Function, and Bioinformatics
Volume
68
Issue
1
Publisher URI
Copyright Statement
© 2007 John Wiley & Sons, Ltd. Self-archiving of the author-manuscript version is not yet supported by this publisher. Please refer to the journal link for access to the definitive, published version or contact the author for more information.
Subject
Mathematical sciences
Biological sciences
Information and computing sciences