| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
Papers In Press, published online ahead of print October 27, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 1X8
Corresponding Author: rmcleod2{at}dal.ca
Apolipoprotein (apo) B48 contains a region (between the carboxyl termini of apo-B22 to –B43) termed the b1 domain that is predicted to be composed of extensive amphipathic b-strands. Pulse-chase analysis of truncated apoB variants revealed that sequences between the carboxyl termini of apo-B37 and -B42 governed the secretion efficiency and intracellular stability of apoB. Thus, while apo-B37, –B34 and –B29 were stable and secreted efficiently, –B42 and –B100 were secreted poorly and were sensitive to degradation. Degradation of –B42 and –B100 could be partially inhibited by the proteasome inhibitor ALLN. Amino acid sequence analysis suggested that a segment encompassing amino acid residues 1724 to 1921 of human apoB (i.e. between the carboxyl termini of apo-B38.0 and –B42.4) was 34% identical and 63% homologous to fatty acid binding proteins, for which crystal structures reveal orthogonal b-sheet structures. To test the hypothesis that sequences from the b1 are involved in apoB degradation, fusion proteins were created that contained apoB29 linked either to fragments derived from the b1 domain of apoB, namely B34-42, B34-37, or B37-42, or to the liver fatty acid binding protein. In transfected cells, the fusion proteins containing the b1 domain segments B34-42 or B37-42 exhibited rapid intracellular degradation, but the fusion proteins containing liver fatty acid binding protein or B34-37 were stable and secreted efficiently. Degradation of fusion proteins containing B34-42 or B37-42 could be blocked by ALLN, and the presence of B34-42 increased the association of the apoB protein with the cytosolic surface of the microsomal membrane. Thus, our data suggest that the presence of specific sequences in the b1 domain of human apoB increases the susceptibility of the protein to rapid intracellular degradation by promoting exposure of the protein to the cytosol, but that not all regions of the b1 domain are functionally equivalent.
Revised on August 13, 2003
Accepted on October 27, 2003
Amino acid sequences within the
1 domain of human apolipoprotein B can mediate rapid intracellular degradation
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  E. A. Fisher, L. R. Lapierre, R. D. Junkins, and R. S. McLeod The AAA-ATPase p97 facilitates degradation of apolipoprotein B by the ubiquitin-proteasome pathway J. Lipid Res., October 1, 2008; 49(10): 2149 - 2160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Burnett, S. Zhong, Z. G. Jiang, A. J. Hooper, E. A. Fisher, R. S. McLeod, Y. Zhao, P. H. R. Barrett, R. A. Hegele, F. M. van Bockxmeer, et al. Missense Mutations in APOB within the beta{alpha}1 Domain of Human APOB-100 Result in Impaired Secretion of ApoB and ApoB-containing Lipoproteins in Familial Hypobetalipoproteinemia J. Biol. Chem., August 17, 2007; 282(33): 24270 - 24283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Whitfield, P. H. R. Barrett, F. M. van Bockxmeer, and J. R. Burnett Lipid Disorders and Mutations in the APOB Gene Clin. Chem., October 1, 2004; 50(10): 1725 - 1732. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
