English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/137572
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Molecular recognition of PTS-1 cargo proteins by Pex5p: implications for protein mistargeting in primary hyperoxaluria

AutorMesa-Torres, Noel; Tomic, Nenad; Albert, Armando ; Salido, Eduardo; Pey, Ángel L.
Palabras claveProtein interactions
Protein import
Primary hyperoxaluria type I
Peroxin 5
Binding energetics
Structure-energetic correlations
Fecha de publicación13-feb-2015
EditorMultidisciplinary Digital Publishing Institute
CitaciónBiomolecules 5(1): 121-141 (2015)
ResumenPeroxisomal biogenesis and function critically depends on the import of cytosolic proteins carrying a PTS1 sequence into this organelle upon interaction with the peroxin Pex5p. Recent structural studies have provided important insights into the molecular recognition of cargo proteins by Pex5p. Peroxisomal import is a key feature in the pathogenesis of primary hyperoxaluria type 1 (PH1), where alanine:glyoxylate aminotransferase (AGT) undergoes mitochondrial mistargeting in about a third of patients. Here, we study the molecular recognition of PTS1 cargo proteins by Pex5p using oligopeptides and AGT variants bearing different natural PTS1 sequences, and employing an array of biophysical, computational and cell biology techniques. Changes in affinity for Pex5p (spanning over 3–4 orders of magnitude) reflect different thermodynamic signatures, but overall bury similar amounts of molecular surface. Structure/energetic analyses provide information on the contribution of ancillary regions and the conformational changes induced in Pex5p and the PTS1 cargo upon complex formation. Pex5p stability in vitro is enhanced upon cargo binding according to their binding affinities. Moreover, we provide evidence that the rational modulation of the AGT: Pex5p binding affinity might be useful tools to investigate mistargeting and misfolding in PH1 by pulling the folding equilibria towards the native and peroxisomal import competent state.
Versión del editorhttp://dx.doi.org/10.3390/biom5010121
Identificadoresissn: 2218-273X
Aparece en las colecciones: (IQFR) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
biomolecules-05-00121.pdf40,33 MBAdobe PDFVista previa
Mostrar el registro completo

Artículos relacionados:

NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.