HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 275, Issue 33, 25547-25555, August 18, 2000

This Article Full Text Full Text (PDF) All Versions of this Article: 275/33/25547    most recent M000431200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schroeder, F. Articles by Kier, A. B. Search for Related Content PubMed PubMed Citation Articles by Schroeder, F. Articles by Kier, A. B. Social Bookmarking                      What's this?

Pro-sterol Carrier Protein-2
ROLE OF THE N-TERMINAL PRESEQUENCE IN STRUCTURE, FUNCTION, AND PEROXISOMAL TARGETING^*

Friedhelm Schroeder^§, Andrey Frolov, Olga Starodub^¶, Barbara B. Atshaves, William Russell, Anca Petrescu, Huan Huang, Adalberto M. Gallegos, Avery McIntosh, Dana Tahotna, David H. Russell, Jeffrey T. Billheimer^**, Charles L. Baum, and Ann B. Kier^¶

From the  Department of Physiology and Pharmacology, ^¶ Department of Pathobiology, and  Department of Chemistry, Texas A & M University, College Station, Texas 77843-4466, the ^** Cardiovascular Department, DuPont Merck Pharmaceutical Company, Experimental Station 400-3231, Wilmington, Delaware 19898-0400, and the  Department of Medicine, Clinical Nutrition Research Unit and Section of Gastroenterology, University of Chicago, Chicago, Illinois 60637

Although the 20-amino acid presequence present in 15-kDa pro-sterol carrier protein-2 (pro-SCP-2, the precursor of the mature 13-kDa SCP-2) alters the function of SCP-2 in lipid metabolism, the molecular basis for this effect is unresolved. The presequence dramatically altered SCP-2 structure as determined by circular dichroism, mass spectroscopy, and antibody accessibility such that pro-SCP-2 had 3-fold less -helix, 7-fold more -structure, 6-fold more reactive C terminus to carboxypeptidase A, 2-fold less binding of anti-SCP-2, and did not enhance sterol transfer from plasma membranes. These differences were not due to protein stability since (i) the same concentration of guanidine hydrochloride was required for 50% unfolding, and (ii) the ligand binding sites displayed the same high affinity (nanomolar K_d values) in the order: cholesterol straight chain fatty acid > kinked chain fatty acid. Laser scanning confocal microscopy and double immunofluorescence demonstrated that pro-SCP-2 was more efficiently targeted to peroxisomes. Transfection of L-cells or McAR7777 hepatoma cells with cDNA encoding pro-SCP-2 resulted in 45% and 59% of SCP-2, respectively, colocalizing with the peroxisomal marker PMP70. In contrast, L-cells transfected with cDNA encoding SCP-2 exhibited 3-fold lower colocalization of SCP-2 with PMP70. In summary, the data suggest for the first time that the 20-amino acid presequence of pro-SCP-2 alters SCP-2 structure to facilitate peroxisomal targeting mediated by the C-terminal SKL peroxisomal targeting sequence.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				D. H. Dyer, V. Wessely, K. T. Forest, and Q. Lan Three-dimensional structure/function analysis of SCP-2-like2 reveals differences among SCP-2 family members J. Lipid Res., March 1, 2008; 49(3): 644 - 653. [Abstract] [Full Text] [PDF]

				M. H. Ko and L. Puglielli The Sterol Carrier Protein SCP-x/Pro-SCP-2 Gene Has Transcriptional Activity and Regulates the Alzheimer Disease {gamma}-Secretase J. Biol. Chem., July 6, 2007; 282(27): 19742 - 19752. [Abstract] [Full Text] [PDF]

				B. P. Atshaves, A. L. McIntosh, D. Landrock, H. R. Payne, J. T. Mackie, N. Maeda, J. Ball, F. Schroeder, and A. B. Kier Effect of SCP-x gene ablation on branched-chain fatty acid metabolism Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G939 - G951. [Abstract] [Full Text] [PDF]

				M.-s. Kim, V. Wessely, and Q. Lan Identification of mosquito sterol carrier protein-2 inhibitors J. Lipid Res., April 1, 2005; 46(4): 650 - 657. [Abstract] [Full Text] [PDF]

				B. P. Atshaves, A. L. McIntosh, H. R. Payne, J. Mackie, A. B. Kier, and F. Schroeder Effect of branched-chain fatty acid on lipid dynamics in mice lacking liver fatty acid binding protein gene Am J Physiol Cell Physiol, March 1, 2005; 288(3): C543 - C558. [Abstract] [Full Text] [PDF]

				D. H. Dyer, S. Lovell, J. B. Thoden, H. M. Holden, I. Rayment, and Q. Lan The Structural Determination of an Insect Sterol Carrier Protein-2 with a Ligand-bound C16 Fatty Acid at 1.35-A Resolution J. Biol. Chem., October 3, 2003; 278(40): 39085 - 39091. [Abstract] [Full Text] [PDF]

				B. P. Atshaves, S. M. Storey, and F. Schroeder Sterol carrier protein-2/sterol carrier protein-x expression differentially alters fatty acid metabolism in L cell fibroblasts J. Lipid Res., September 1, 2003; 44(9): 1751 - 1762. [Abstract] [Full Text] [PDF]

				B. P. Atshaves, S. M. Storey, A. Petrescu, C. C. Greenberg, O. I. Lyuksyutova, R. Smith III, and F. Schroeder Expression of fatty acid binding proteins inhibits lipid accumulation and alters toxicity in L cell fibroblasts Am J Physiol Cell Physiol, September 1, 2002; 283(3): C688 - C703. [Abstract] [Full Text] [PDF]

				A. D. Petrescu, R. Hertz, J. Bar-Tana, F. Schroeder, and A. B. Kier Ligand Specificity and Conformational Dependence of the Hepatic Nuclear Factor-4alpha (HNF-4alpha ) J. Biol. Chem., June 28, 2002; 277(27): 23988 - 23999. [Abstract] [Full Text] [PDF]

				F. Schroeder, A. M. Gallegos, B. P. Atshaves, S. M. Storey, A. L. McIntosh, A. D. Petrescu, H. Huang, O. Starodub, H. Chao, H. Yang, et al. Recent Advances in Membrane Microdomains: Rafts, Caveolae, and Intracellular Cholesterol Trafficking Experimental Biology and Medicine, November 1, 2001; 226(10): 873 - 890. [Abstract] [Full Text] [PDF]

				B. P. Atshaves, S. M. Storey, A. L. McIntosh, A. D. Petrescu, O. I. Lyuksyutova, A. S. Greenberg, and F. Schroeder Sterol Carrier Protein-2 Expression Modulates Protein and Lipid Composition of Lipid Droplets J. Biol. Chem., June 29, 2001; 276(27): 25324 - 25335. [Abstract] [Full Text] [PDF]

				A. D. Petrescu, A. M. Gallegos, Y. Okamura, J. F. Strauss III, and F. Schroeder Steroidogenic Acute Regulatory Protein Binds Cholesterol and Modulates Mitochondrial Membrane Sterol Domain Dynamics J. Biol. Chem., September 28, 2001; 276(40): 36970 - 36982. [Abstract] [Full Text] [PDF]