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Plos Biology : Molecular Requirements for Peroxisomal Targeting of Alanine-glyoxylate Aminotransferase as an Essential Determinant in Primary Hyperoxaluria Type 1, Volume 10

By Hughson, Frederick

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Book Id: WPLBN0003922335
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Biology : Molecular Requirements for Peroxisomal Targeting of Alanine-glyoxylate Aminotransferase as an Essential Determinant in Primary Hyperoxaluria Type 1, Volume 10  
Author: Hughson, Frederick
Volume: Volume 10
Language: English
Subject: Journals, Science, Biology
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Biology
Historic
Publication Date:
Publisher: Plos

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Hughson, F. (n.d.). Plos Biology : Molecular Requirements for Peroxisomal Targeting of Alanine-glyoxylate Aminotransferase as an Essential Determinant in Primary Hyperoxaluria Type 1, Volume 10. Retrieved from http://worldebooklibrary.org/


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Description : Alanine-glyoxylate aminotransferase is a peroxisomal enzyme, of which various missense mutations lead to irreversible kidney damage via primary hyperoxaluria type 1, in part caused by improper peroxisomal targeting. To unravel the molecular mechanism of its recognition by the peroxisomal receptor Pex5p, we have determined the crystal structure of the respective cargo–receptor complex. It shows an extensive protein/protein interface, with contributions from residues of the peroxisomal targeting signal 1 and additional loops of the C-terminal domain of the cargo. Sequence segments that are crucial for receptor recognition and hydrophobic core interactions within alanine-glyoxylate aminotransferase are overlapping, explaining why receptor recognition highly depends on a properly folded protein. We subsequently characterized several enzyme variants in vitro and in vivo and show that even minor protein fold perturbations are sufficient to impair Pex5p receptor recognition. We discuss how the knowledge of the molecular parameters for alanine-glyoxylate aminotransferase required for peroxisomal translocation could become useful for improved hyperoxaluria type 1 treatment.

 

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