Abstract
The microsomal triglyceride transfer protein (MTTP) is essential for the assembly of VLDLs. We recently observed that a polymorphism in the MTTP promoter (-493G>T), which is in allelic association with an isoleucine-to-theronine substitution at position 128 (Ile128Thr) in the expressed protein, confers an increased risk of coronary heart disease. Two variant proteins comprising amino acids 16-297 of intact MTTP, MTTP(N)-Ile128 and MTTP(N)-Thr128, had similar native secondary structure content, as judged by circular dichroism. However, the thermal stability of MTTP(N)-Thr128 was greatly reduced, and this protein was also more extensively cleaved in limited proteolysis experiments compared with MTTP(N)-Ile128; both of these findings support a less compact fold. On adding LDL, which includes natively folded apolipoprotein B (apoB), decreased stability of the MTTP(N)-Thr128-LDL complex was observed compared with that of the MTTP(N)-Ile128-LDL complex. In a refined model of the N-terminal domain of MTTP, residue 128 is located in a surface-exposed position, in the same region as an identified MTTP binding site in the homologous apoB protein. Thus, the Ile128Thr polymorphism confers reduced structural stability, leading to decreased ...Continue Reading
References
May 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·O U BegS S Fojo
Jan 1, 1989·Progress in Biophysics and Molecular Biology·B M ByrneG Ab
Feb 28, 1986·Biochimica Et Biophysica Acta·J R Wetterau, D B Zilversmit
Mar 1, 1995·The Journal of Clinical Investigation·L J BaierM Prochazka
Nov 11, 1994·Nucleic Acids Research·J D ThompsonT J Gibson
Aug 2, 1994·Proceedings of the National Academy of Sciences of the United States of America·D A GordonJ Wetterau
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Jun 1, 1993·Protein Engineering·M A AndradeF Morán
Feb 11, 1997·Biochemistry·M E Hodsdon, D P Cistola
Aug 14, 1997·Nature·M S BrownJ L Goldstein
Apr 29, 1998·The Journal of Clinical Investigation·J BorénS G Young
May 23, 1998·Arteriosclerosis, Thrombosis, and Vascular Biology·F KarpeA Hamsten
Jul 17, 1998·Circulation·L B NielsenS G Young
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·D M MitchellE A Fisher
Jan 8, 1999·Journal of Molecular Biology·C J MannC C Shoulders
Jun 22, 2000·Journal of Molecular Biology·L A KelleyM J Sternberg
Sep 29, 2000·Biochemistry·C NeylonN E Dixon
Dec 29, 2000·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·R H Unger, L Orci
May 19, 2001·The Journal of Biological Chemistry·J Liang, H N Ginsberg
Aug 2, 2001·The Journal of Biological Chemistry·J BjorkegrenS G Young
Nov 13, 2001·The Journal of Biological Chemistry·Meihui PanHenry N Ginsberg
Jun 19, 2002·The Journal of Biological Chemistry·Christofer FloodJan Borén
Jul 24, 2002·Biochemistry·James R Thompson, Leonard J Banaszak
May 1, 1959·Archives of Biochemistry and Biophysics·G L ELLMAN
Mar 9, 2004·Progress in Lipid Research·James A Hamilton
May 12, 2004·Circulation·Helena LedmyrUNKNOWN WOSCOPS executive
Citations
Mar 29, 2011·DNA and Cell Biology·Mohammad HashemiSara Shafieipour
Apr 24, 2013·Journal of Clinical Psychopharmacology·Ying-Jay LiouChen-Jee Hong
Apr 24, 2012·Journal of Tropical Medicine·Rodrigo Gurgel-GonçalvesA Townsend Peterson
Jun 24, 2009·Journal of Lipid Research·Anna AminoffEwa Ehrenborg
Feb 6, 2014·Genes & Nutrition·Karina MeidtnerHeiner Boeing
Mar 6, 2009·European Journal of Gastroenterology & Hepatology·Dae Won JunJeong Don Chae
Jan 18, 2007·Expert Opinion on Therapeutic Targets·John R Burnett, Gerald F Watts
Mar 4, 2009·Annals of Human Biology·K E LuévanoM T Magaña
Oct 28, 2008·Molecular Genetics and Metabolism·Mike BöhmeUNKNOWN KORA Study Cohort
May 1, 2007·Biochemistry and Molecular Biology Education : a Bimonthly Publication of the International Union of Biochemistry and Molecular Biology·Annelie BraunerEwa Ehrenborg
Sep 15, 2007·Human Mutation·Diana RubinFrank Döring
Jun 7, 2013·Liver International : Official Journal of the International Association for the Study of the Liver·Xian E PengXu Lin
Oct 16, 2015·BMC Medical Genetics·Pi-Jung HsiaoKung-Kai Kuo
Feb 11, 2015·Lipids·Yingying TianDongsheng Ouyang
Aug 4, 2016·Biochimica Et Biophysica Acta·Meghan T WalshM Mahmood Hussain
Oct 4, 2016·Critical Reviews in Clinical Laboratory Sciences·Meghan T Walsh, M Mahmood Hussain
Aug 1, 2015·Circulation. Cardiovascular Genetics·Meghan T WalshM Mahmood Hussain
Jul 29, 2020·Saudi Journal of Gastroenterology : Official Journal of the Saudi Gastroenterology Association·Jie TanYongning Xin
May 14, 2016·Journal of Atherosclerosis and Thrombosis·Genovefa D KolovouGerald F Watts