Disease-causing mutations in cardiac troponin T: identification of a critical tropomyosin-binding region

Biophysical Journal
Thomas PalmN J Greenfield

Abstract

Fifteen percent of the mutations causing familial hypertrophic cardiomyopathy are in the troponin T gene. Most mutations are clustered between residues 79 and 179, a region known to bind to tropomyosin at the C-terminus near the complex between the N- and C-termini. Nine mutations were introduced into a troponin T fragment, Gly-hcTnT(70-170), that is soluble, alpha-helical, binds to tropomyosin, promotes the binding of tropomyosin to actin, and stabilizes an overlap complex of N-terminal and C-terminal tropomyosin peptides. Mutations between residues 92 and 110 (Arg92Leu, Arg92Gln, Arg92Trp, Arg94Leu, Ala104Val, and Phe110Ile) impair tropomyosin-dependent functions of troponin T. Except for Ala104Val, these mutants bound less strongly to a tropomyosin affinity column and were less able to stabilize the TM overlap complex, effects that were correlated with increased stability of the troponin T, measured using circular dichroism. All were less effective in promoting the binding of tropomyosin to actin. Mutations within residues 92-110 may cause disease because of altered interaction with tropomyosin at the overlap region, critical for cooperative actin binding and regulatory function. A model for a five-chained coiled-coil for tr...Continue Reading

References

Jun 1, 1979·Biophysical Journal·P Y Chou, G D Fasman
Mar 29, 1979·Nature·G N PhillipsC Cohen
Oct 1, 1977·Canadian Journal of Biochemistry·J R Pearlstone, L B Smillie
Oct 25, 1975·Journal of Molecular Biology·A D McLachlan, M Stewart
Oct 1, 1975·The Biochemical Journal·P JacksonS V Perry
Jan 1, 1990·Methods in Enzymology·F W StudierJ W Dubendorff
Feb 4, 1987·Nature·S P WhiteG N Phillips
Jun 18, 1985·Biochemistry·S E Hitchcock-DeGregoriT M Chou
Jan 15, 1974·Biochemistry·P Y Chou, G D Fasman
Jan 1, 1972·Cold Spring Harbor Symposia on Quantitative Biology·C CohenR M Lucas
Jan 1, 1982·Advances in Biophysics·I Ohtsuki, K Nagano
Dec 5, 1982·Journal of Molecular Biology·P F FlickerC Cohen
Apr 20, 1995·The New England Journal of Medicine·H WatkinsJ G Seidman
Feb 23, 1996·The Journal of Biological Chemistry·R L Hammell, S E Hitchcock-DeGregori
Mar 1, 1997·Journal of the American College of Cardiology·J C MoolmanH Watkins
Feb 1, 1997·Journal of Molecular and Cellular Cardiology·C Nakajima-TaniguchiK Yamauchi-Takihara
Oct 23, 1997·Biophysical Journal·D Cabral-LillyC Cohen
Sep 19, 1998·Circulation Research·G BonneK Schwartz
Sep 22, 1998·Journal of Muscle Research and Cell Motility·S V Perry
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·H L SweeneyH Watkins
Aug 17, 1999·The Journal of Clinical Investigation·J C TardiffL A Leinwand
Sep 25, 1999·The Journal of Biological Chemistry·L S TobacmanE Homsher
Oct 21, 1999·Biochemistry·P MukherjeaS E Hitchcock-DeGregori

❮ Previous
Next ❯

Citations

Jun 25, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Julien Ochala
Sep 28, 2006·Biochemistry·Alla S KostyukovaBrian A Rapp
Jul 30, 2011·Biochemistry·Edward P ManningSteven D Schwartz
Oct 16, 2012·The Journal of Biological Chemistry·Devanand Kowlessur, Larry S Tobacman
Nov 7, 2008·Cardiovascular Research·Joanne S Ingwall
Dec 7, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Jesus Jimenez, Jil C Tardiff
Jun 9, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Pia J GuintoJil C Tardiff
Sep 4, 2003·The Journal of Clinical Investigation·Ketty Schwartz, Jean-Jacques Mercadier
Jul 25, 2009·PloS One·Abhishek Singh, Sarah E Hitchcock-Degregori
Jan 6, 2005·The Japanese Journal of Physiology·K Harada, S Morimoto
Dec 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Briar R Ertz-BergerJil C Tardiff
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yu LiCarolyn Cohen
Apr 20, 2014·Journal of Muscle Research and Cell Motility·Athanasia KalyvaPanos E Vardas
Dec 11, 2014·Pharmacogenomics·Anastasios LymperopoulosKarlee Walklett
Aug 14, 2012·Journal of Molecular and Cellular Cardiology·Steven J FordMurali Chandra
Aug 31, 2010·Clinica Chimica Acta; International Journal of Clinical Chemistry·Gilles MillatRobert Rousson
Jul 9, 2008·International Journal of Cardiology·Feng JuanZhang Lianfeng
Mar 10, 2016·Proceedings of the National Academy of Sciences of the United States of America·Michael R WilliamsSteven D Schwartz
Apr 30, 2003·Biophysical Journal·Thomas PalmSarah E Hitchcock-DeGregori
Oct 7, 2004·Molecular Genetics and Metabolism·Christopher B StefanelliMark W Russell
Sep 27, 2006·Journal of Molecular Biology·Norma J GreenfieldSarah E Hitchcock-DeGregori
Jul 17, 2003·American Journal of Human Genetics·Sandy S SungMichael Bamshad
Nov 26, 2003·The American Journal of Cardiology·Francesca TorricelliFranco Cecchi
May 15, 2012·Journal of Molecular Biology·Edward P ManningSteven D Schwartz
Nov 17, 2009·Journal of Molecular and Cellular Cardiology·Ruth H WillottJames D Potter

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.