Oligomerization capacity of two arylsulfatase A mutants: C300F and P425T

• Type: Article in International Scientific Journal
• Date: 2003

Authors

marcao, a (Author) Other; azevedo, je (Author) ICBAS; gieselmann, v (Author) Other; miranda, mcs (Author) Other

Journal

Title: Biochemical and Biophysical Research Communications

Vol. 306

Pages: 293-297

ISSN: 0006-291X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 5 Citations

Other information

Authenticus ID: P-000-G8P

DOI: 10.1016/S0006-291X(03)00969-0

Abstract (EN): Arylsulfatase A (ARSA) is a lysosomal enzyme implicated in most cases of metachromatic leukodystrophy (MLD). The quaternary structure of ARSA is pH-dependent: at neutral pH, ARSA is a. homodimeric protein; at lysosomal (acidic) pH, ARSA is homo-octameric. This dimer-octamer transition seems to be of major importance for the stability of the enzyme in the lysosomal milieu. Sedimentation analysis was used to study the oligomerization capacity of C300F and P425T-substituted ARSA, two MLD-associated forms of the enzyme displaying reduced lysosomal half-lives. P425T-ARSA displays a modest reduction in its octamerization capacity. In contrast, the C300F mutation strongly interferes with the octamerization process of ARSA but not with its dimerization capacity. Interestingly, a major fraction of dimeric ARSA-C300F is composed of covalently linked ARSA molecules, through a thiol-cleavable bond that probably involves Cys414 residues from each monomer. Our data support the notion that the reduced lysosomal half-life of some mutated forms of ARSA is related to deficient octamerization. (C) 2003 Elsevier Science (USA). All rights reserved.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5