Journal of Lipid Research, Vol 38, 1149-1162, Copyright © 1997 by Lipid Research, Inc.

ARTICLES

Asymmetric distribution of pause transfer sequences in apolipoprotein B- 100

MH Kivlen, CA Dorsey, VR Lingappa and RS Hegde
Department of Physiology, University of California, San Francisco 94143, USA.

Lipoprotein assembly requires a complex and regulated set of events that includes apolipoprotein B (apoB) translocation across the endoplasmic reticulum (ER) membrane, folding, and association with lipids. Unlike simple secretory proteins which are cotranslationally translocated directly into the ER lumen, nascent apoB contains pause transfer (PT) sequences that direct the transient stopping and subsequent restarting of its translocation, a phenomenon termed translocational pausing. During one particular translocational pause in apoB, the ribosome-membrane junction and ER translocation channel have been shown to be altered in such a way as to expose the nascent polypeptide to the cytosol and direct a change in the proteins neighboring the nascent chain. In this study, we have experimentally identified the location and distribution of the translocational pauses that are present throughout apoB-100. We find that pause transfer sequences are distributed asymmetrically, clustering in three distinct domains: a) nine functional PT sequences appear in the amino terminal 20% of apoB, b) four more PT sequences occur just before the end of apoB-48, and c) an additional ten PT sequences are found between apoB- 65-95. These clusters are interrupted by two lipid binding regions of approximately 100 kD each in which no PT sequences occur. The implications of this asymmetric distribution of PT sequences, and their correlation with previously hypothesized structural and functional domains of apoB, are discussed.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Yamaguchi, D. M. Conlon, J. J. Liang, E. A. Fisher, and H. N. Ginsberg Translocation Efficiency of Apolipoprotein B Is Determined by the Presence of beta-Sheet Domains, Not Pause Transfer Sequences J. Biol. Chem., September 15, 2006; 281(37): 27063 - 27071. [Abstract] [Full Text] [PDF]

				Z. Li, Y. Kako, L. Pang, M. W. Freeman, J. M. Glick, X. Wang, and I. J. Goldberg Effects of overexpression of the amino-terminal fragment of apolipoprotein B on apolipoprotein B and lipoprotein production J. Lipid Res., December 1, 2000; 41(12): 1912 - 1920. [Abstract] [Full Text]

				X. F. Huang and G. S. Shelness Efficient glycosylation site utilization by intracellular apolipoprotein B: implications for proteasomal degradation J. Lipid Res., December 1, 1999; 40(12): 2212 - 2222. [Abstract] [Full Text] [PDF]

				J.-s. Liang, X. Wu, H. Jiang, M. Zhou, H. Yang, P. Angkeow, L.-S. Huang, S. L. Sturley, and H. Ginsberg Translocation Efficiency, Susceptibility to Proteasomal Degradation, and Lipid Responsiveness of Apolipoprotein B Are Determined by the Presence of beta  Sheet Domains J. Biol. Chem., December 25, 1998; 273(52): 35216 - 35221. [Abstract] [Full Text] [PDF]

				A. E. Rusiñol, R. S. Hegde, S. L. Chuck, V. R. Lingappa, and J. E. Vance Translocational pausing of apolipoprotein B can be regulated by membrane lipid composition J. Lipid Res., June 1, 1998; 39(6): 1287 - 1294. [Abstract] [Full Text]

				X. Du, J. Daniel Stoops, J. R. Mertz, C. Michael Stanley, and J. L. Dixon Identification of Two Regions in Apolipoprotein B100 that are Exposed on the Cytosolic Side of the Endoplasmic Reticulum Membrane J. Cell Biol., May 4, 1998; 141(3): 585 - 599. [Abstract] [Full Text] [PDF]

				J.-s. Liang, X. Wu, E. A. Fisher, and H. N. Ginsberg The Amino-terminal Domain of Apolipoprotein B Does Not Undergo Retrograde Translocation from the Endoplasmic Reticulum to the Cytosol. PROTEASOMAL DEGRADATION OF NASCENT APOLIPOPROTEIN B BEGINS AT THE CARBOXYL TERMINUS OF THE PROTEIN, WHILE APOLIPOPROTEIN B IS STILL IN ITS ORIGINAL TRANSLOCON J. Biol. Chem., October 6, 2000; 275(41): 32003 - 32010. [Abstract] [Full Text] [PDF]

				R. Pariyarath, H. Wang, J. D. Aitchison, H. N. Ginsberg, W. J. Welch, A. E. Johnson, and E. A. Fisher Co-translational Interactions of Apoprotein B with the Ribosome and Translocon during Lipoprotein Assembly or Targeting to the Proteasome J. Biol. Chem., January 5, 2001; 276(1): 541 - 550. [Abstract] [Full Text] [PDF]