| http://purl.uniprot.org/citations/34116124 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34116124 | http://www.w3.org/2000/01/rdf-schema#comment | "MPV17 is an integral inner mitochondrial membrane protein, whose loss-of-function is linked to the hepatocerebral form of the mitochondrial-DNA-depletion syndrome, leading to a tissue-specific reduction of mitochondrial DNA and organ failure in infants. Several disease-causing mutations in MPV17 have been identified and earlier studies with reconstituted protein suggest that MPV17 forms a high conductivity channel in the membrane. However, the molecular and structural basis of the MPV17 functionality remain only poorly understood. In order to make MPV17 accessible to high-resolution structural studies, we here present an efficient protocol for its high-level production in E. coli and refolding into detergent micelles. Using biophysical and NMR methods, we show that refolded MPV17 in detergent micelles adopts a compact structure consisting of six membrane-embedded α-helices. Furthermore, we demonstrate that MPV17 forms oligomers in a lipid bilayer that are further stabilized by disulfide-bridges. In line with these findings, MPV17 could only be inserted into lipid nanodiscs of 8-12 nm in diameter if intrinsic cysteines were either removed by mutagenesis or blocked by chemical modification. Using this nanodisc reconstitution approach, we could show that disease-linked mutations in MPV17 abolish its oligomerization properties in the membrane. These data suggest that, induced by oxidative stress, MPV17 can alter its oligomeric state from a properly folded monomer to a disulfide-stabilized oligomeric pore which might be required for the transport of metabolic DNA precursors into the mitochondrial matrix to compensate for the damage caused by reactive oxygen species."xsd:string |
| http://purl.uniprot.org/citations/34116124 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2021.167098"xsd:string |
| http://purl.uniprot.org/citations/34116124 | http://purl.uniprot.org/core/author | "Hagn F."xsd:string |
| http://purl.uniprot.org/citations/34116124 | http://purl.uniprot.org/core/author | "Sperl L.E."xsd:string |
| http://purl.uniprot.org/citations/34116124 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34116124 | http://purl.uniprot.org/core/name | "J Mol Biol"xsd:string |
| http://purl.uniprot.org/citations/34116124 | http://purl.uniprot.org/core/pages | "167098"xsd:string |
| http://purl.uniprot.org/citations/34116124 | http://purl.uniprot.org/core/title | "NMR Structural and Biophysical Analysis of the Disease-Linked Inner Mitochondrial Membrane Protein MPV17."xsd:string |
| http://purl.uniprot.org/citations/34116124 | http://purl.uniprot.org/core/volume | "433"xsd:string |
| http://purl.uniprot.org/citations/34116124 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34116124 |
| http://purl.uniprot.org/citations/34116124 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34116124 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z466-mappedCitation-34116124 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34116124 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z469-mappedCitation-34116124 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34116124 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z3Z9-mappedCitation-34116124 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34116124 |
| http://purl.uniprot.org/uniprot/#_B5MC10-mappedCitation-34116124 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34116124 |
| http://purl.uniprot.org/uniprot/#_B5MC53-mappedCitation-34116124 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34116124 |
| http://purl.uniprot.org/uniprot/#_P39210-mappedCitation-34116124 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34116124 |
| http://purl.uniprot.org/uniprot/#_G5E9F5-mappedCitation-34116124 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34116124 |
| http://purl.uniprot.org/uniprot/#_Q9UPC7-mappedCitation-34116124 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34116124 |
| http://purl.uniprot.org/uniprot/G5E9F5 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34116124 |
| http://purl.uniprot.org/uniprot/A0A0S2Z3Z9 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34116124 |
| http://purl.uniprot.org/uniprot/P39210 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34116124 |
| http://purl.uniprot.org/uniprot/A0A0S2Z469 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34116124 |
| http://purl.uniprot.org/uniprot/B5MC53 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34116124 |