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Titolo:
TOPOLOGY OF ATP-BINDING DOMAIN OF ADRENOLEUKODYSTROPHY GENE-PRODUCT IN PEROXISOMES
Autore:
CONTRERAS M; SENGUPTA TK; SHEIKH F; AUBOURG P; SINGH I;
Indirizzi:
MED UNIV S CAROLINA,DEPT PEDIAT,DIV NEUROGENET,171 ASHLEY AVE CHARLESTON SC 29425 MED UNIV S CAROLINA,DEPT PEDIAT,DIV NEUROGENET CHARLESTON SC 29425 HOSP ST VINCENT DE PAUL,INSERM U342 F-75014 PARIS FRANCE
Titolo Testata:
Archives of biochemistry and biophysics
fascicolo: 2, volume: 334, anno: 1996,
pagine: 369 - 379
SICI:
0003-9861(1996)334:2<369:TOADOA>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
X-LINKED ADRENOLEUKODYSTROPHY; LIGNOCEROYL-COA LIGASES; CHAIN FATTY-ACIDS; MEMBRANE-PROTEIN; RAT-LIVER; OXIDATION; LOCALIZATION; FIBROBLASTS; MUTATIONS; IDENTIFICATION;
Keywords:
PEROXISOMES; ADRENOLEUKODYSTROPHY; ATP-BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
M. Contreras et al., "TOPOLOGY OF ATP-BINDING DOMAIN OF ADRENOLEUKODYSTROPHY GENE-PRODUCT IN PEROXISOMES", Archives of biochemistry and biophysics, 334(2), 1996, pp. 369-379

Abstract

Adrenoleukodystrophy (X-ALD)is a demyelinating disorder characterizedby the accumulation of saturated very-long-chain fatty acids (> C-22:0) due to the impaired activity of lignoceroyl-CoA ligase. The gene responsible for the disease was found to code for a 84-kDa peroxisomal integral membrane protein. Its amino acid sequence has high homology with the ATP-binding cassette superfamily of transporters and it is predicted to have six membrane-spanning segments and a putative ATP-binding domain. To define the function of ALDP, we studied the topology of its ATP-binding domain by using antibodies (1D6) against a hydrophobic domain (amino acid residues 279 to 482) and antibodies (Abet) against the C-terminal 15-amino-acid hydrophilic domain (amino acid residues 731 to 745) of ALDP. The observation of punctate fluorescence in permeabilized ALD fibroblasts, using Abet antibodies but not with antibodiesagainst catalase, suggests that the C-terminal segment of ALDP is projected toward the cytoplasm from the peroxisomal membrane. Trypsinization of intact peroxisomes under isotonic conditions abolishes the Abetantibody recognition site, whereas the 1D6 antibodies identify a degradation product of 43-kDa protein that has been protected and retainedby the membrane. This again suggests that the C-terminal portion of the ALDP protein is located on the outside (cytoplasmic) face of the peroxisomal membrane, Additional support for this conclusion was obtained by purification of the ALDP C-terminal domain, released from purified rat liver peroxisomes incubated with the cytosolic fraction, using blue-Sepharose affinity chromatography. A 47-kDa peptide retained by the column was recognized by Western blot analysis with Abet antibodies against the C-terminal sequence of ALDP and this polypeptide on polyvinylidene difluoride membrane was able to bind [gamma-P-32]ATP in vitroin the presence of Mg2+. These results demonstrate that the C-terminal peptide containing the ATP-binding domains of ALDP is on the cytoplasmic surface of the peroxisomal membrane where this domain may function as an ATPase to support the functional role of ALDP in the peroxisomal membrane. (C) 1996 Academic Press, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/11/20 alle ore 20:36:52