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dc.contributor.authorMesa-Torres, Noeles_ES
dc.contributor.authorTomic, Nenades_ES
dc.contributor.authorAlbert, Armandoes_ES
dc.contributor.authorSalido, Eduardoes_ES
dc.contributor.authorPey, Ángel L.es_ES
dc.identifier.citationMesa-Torres, N. [et al]. Molecular Recognition of PTS-1 Cargo Proteins by Pex5p: Implications for Protein Mistargeting in Primary Hyperoxaluria. Biomolecules 2015, 5, 121-141. []es_ES
dc.description.abstractPeroxisomal 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.es_ES
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs 3.0 Licensees_ES
dc.subjectProtein importes_ES
dc.subjectPrimary hyperoxaluria type Ies_ES
dc.subjectPeroxin 5es_ES
dc.subjectProtein interactionses_ES
dc.subjectBiding energeticses_ES
dc.subjectStructura-energetic correlationses_ES
dc.titleMolecular Recognition of PTS-1 Cargo Proteins by Pex5p: Implications for Protein Mistargeting in Primary Hyperoxaluriaes_ES

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