Nav: Home

Scientists identify a key mechanism regulating a protein required for muscle and heart function

January 12, 2018

Scientists at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) and Columbia University in New York have discovered an important mechanism in the regulation of a protein that plays an essential role in the function of skeletal muscle and the heart. The study, published today in Nature Communications and coordinated by CNIC researcher Jorge Alegre-Cebollada, describes a new mechanism in the regulation of the elasticity of the giant protein titin. Titin, explained Alegre-Cebollada, is a key protein in the functioning of striated muscles throughout the body, particularly in the heart: "the proof of this is that mutations in the titin gene are a common cause of diseases affecting the muscles of the body and the heart."

Titin is the largest protein in the human body and as such has a multitude of functions. According to Jorge Alegre-Cebollada, "in simple terms we can think of titin as a 'molecular spring' that allows muscle cells to contract in synchrony." However, it is not a simple spring, and the many mechanisms that determine titin elasticity include the unfolding of specific regions in its structure called immunoglobulin domains. In all, titin elasticity is determined by the concerted action of more than 100 immunoglobulin domains within the protein.

Using bioinformatic and structural biology approaches, the research team found that the immunoglobulin domains have a high cysteine content. This amino acid confers special properties. Jorge Alegre-Cebollada explained that "when 2 cyteines in a protein come close to one another, they can form a chemical link between different parts of the polypeptide chain called a disulfide bond." The researchers observed that many of the immunoglobulin domains in titin form disulfide links and that the cysteines participating in them can change dynamically, a process called isomerization. "The most interesting finding was that the formation and isomerization of disulfide bonds causes major changes in the elastic properties of titin."

The formation of disulfide bonds is an example of a broader class of biochemical transformations known as reduction-oxidation (redox). It has long been known that many disease processes affecting the heart, including myocardial infarction, involve sudden and drastic changes in the redox state of the heart muscle.

Dr. Alegre-Cebollada's group is currently investigating how our cells modify the titin redox state as a mechanism to modulate skeletal and heart muscle activity and how different diseases can interfere with the mechanical action of the protein, resulting in loss of functionality. Alegre-Cebollada concludes, "Our mechanical findings were made possible by reconstituting contractile systems in vitro. While we have learned a lot through this approach, the challenge now is to understand how these basic principles operate in a living organism. This is the focus of our current research, using a multidisciplinary approach that combines advanced techniques in physiology, biology, and biochemistry."

The study is the result of a collaboration between Dr. Alegre-Cebollada and Professor Julio Fernández at Columbia University. Professor Fernández is a pioneer in the development of single-molecule biophysical techniques for investigating the mechanical properties of proteins, and his collaboration with Dr. Alegre-Cebollada has made it possible to describe the biochemical regulation of protein mechanics.

Centro Nacional de Investigaciones Cardiovasculares

Related Protein Articles:

Hi-res view of protein complex shows how it breaks up protein tangles
A new, high-resolution view of the structure of Hsp104 (heat shock protein 104), a natural yeast protein nanomachine with six subunits, may show news ways to dismantle harmful protein clumps in disease.
Breaking the protein-DNA bond
A new Northwestern University study finds that unbound proteins in a cell break up protein-DNA bonds as they compete for the single-binding site.
FASEB Science Research Conference: Protein Kinases and Protein Phosphorylation
This conference focuses on the biology of protein kinases and phosphorylation signaling.
Largest resource of human protein-protein interactions can help interpret genomic data
An international research team has developed the largest database of protein-to-protein interaction networks, a resource that can illuminate how numerous disease-associated genes contribute to disease development and progression.
STAT2: Much more than an antiviral protein
A protein known for guarding against viral infections leads a double life, new research shows, and can interfere with cell growth and the defense against parasites.
A protein makes the difference
It is well-established knowledge that blood vessels foster the growth of tumors.
Nuclear protein causes neuroblastoma to become more aggressive
Aggressive forms of neuroblastoma contain a specific protein in their cells' nuclei that is not found in the nuclei of more benign forms of the cancer, and the discovery, made through research from the University of Rochester Medical Center, could lead to new forms of targeted therapy.
How a protein could become the next big sweetener
High-fructose corn syrup and sugar are on the outs with calorie-wary consumers.
High animal protein intake associated with higher, plant protein with lower mortality rate
The largest study to examine the effects of different sources of dietary protein found that a high intake of proteins from animal sources -- particularly processed and unprocessed red meats -- was associated with a higher mortality rate, while a high intake of protein from plant sources was associated with a lower risk of death.
Protein in, ammonia out
A recent study has compiled and analyzed data from 25 previous studies.

Related Protein Reading:

Protein Power: The High-Protein/Low Carbohydrate Way to Lose Weight, Feel Fit, and Boost Your Health-in Just Weeks!
by Michael R. Eades (Author), Mary Dan Eades (Author)

New York Times Bestseller - An effective, medically sound diet that lets you eat bacon, eggs, steak, even cheese? It's true!  Lose fat.  Feel fit.  Stop craving.  Without counting fat grams and without giving up the foods you love. Includes recipes for healthy meals to lose weight.

Based on cutting-edge research, this revolutionary and deliciously satisfying plan has already helped thousands of patients lose weight and achieve other lifesaving health benefits, including lower cholesterol and blood pressure readings and an improvement or reversal of common... View Details

Clean Protein: The Revolution that Will Reshape Your Body, Boost Your Energy—and Save Our Planet
by Kathy Freston (Author), Bruce Friedrich (Author)

Join the CLEAN PROTEIN revolution and lose weight, feel stronger, and live longer.

Food and wellness experts Kathy Freston and Bruce Friedrich have spent years researching the future of protein. They've talked to the food pioneers and the nutrition scientists, and now they've distilled what they've learned into a strength-building plan poised to reshape your body and change your world.

Complete with delicious recipes and a detailed guide to food planning, Clean Protein explains everything you need to know in order to get lean, gain energy, and stay mentally sharp.... View Details

Proteins: Structure and Function
by David Whitford (Author)

Proteins: Structure and Function is a comprehensive introduction to the study of proteins and their importance to modern biochemistry. Each chapter addresses the structure and function of proteins with a definitive theme designed to enhance student understanding. Opening with a brief historical overview of the subject the book moves on to discuss the ‘building blocks’ of proteins and their respective chemical and physical properties. Later chapters explore experimental and computational methods of comparing proteins, methods of protein purification and protein folding and... View Details

The Bariatric Foodie Guide to Perfect Protein Shakes (Volume 1)
by Ms Nikki L Massie (Author)

Life can be stressful. Your protein shake shouldn't be! Dozens of crave-worthy protein drink recipes tips & tricks from popular weight-loss surgery blog, Bariatric Foodie! View Details

Proteins (Explore the molecules of life)
by Tali Lavy (Author), Ofir Corcos (Illustrator)

The human body relies on proteins for many of its most important processes. When we contract our muscles, we use proteins. We need proteins to fight disease and help blood cells transport oxygen. Proteins are the building blocks of life, and what’s more, they’re fascinating.

Written by structural biologist Tali Lavy, this book is a playfully illustrated exploration of proteins and their importance in human biology. Children will learn how proteins are composed of amino acids, how DNA encodes proteins, and how proteins affect life at a molecular level. Entertaining drawings of... View Details

Plant-Protein Recipes That You’ll Love: Enjoy the goodness and deliciousness of 150+ healthy plant-protein recipes!
by Carina Wolff (Author)

Discover affordable, all-natural plant-based protein recipes that taste good and improve your health in this unique and easy cookbook.

Plant-based proteins are a healthier, more nutritious, and more environmentally friendly alternative to animal protein. But you don’t have to be a vegan or dedicated vegetarian to enjoy the benefits of a plant-based diet. Whether you’re going meatless full time, part time, or only occasionally, you’ll easily find a recipe to power your day.

From hearty breakfasts to satisfying dinners, this cookbook features 150 delicious, budget-friendly,... View Details

The Protein Counter 3rd Edition
by Jo-Ann Heslin M.A. R.D. CDN (Author), Karen J Nolan Ph.D. (Author)



Put the latest protein recommendations to work for you.

Every day your body must build and replace millions of cells—an impossible job without proteins. The amount you need changes with exercise, stress, weight loss, illness, injury, and pregnancy. That’s why your body is counting on you to eat the proteins it needs to maximize fitness, boost your immune system, protect you from chronic disease, help you lose weight and keep it off, and much more. The completely revised and updated Protein... View Details

Protein Actions: Principles and Modeling
by Ivet Bahar (Author), Robert L. Jernigan (Author), Ken A. Dill (Author)

Protein Actions: Principles and Modeling is aimed at graduates, advanced undergraduates, and any professional who seeks an introduction to the biological, chemical, and physical properties of proteins. Broadly accessible to biophysicists and biochemists, it will be particularly useful to student and professional structural biologists and molecular biophysicists, bioinformaticians and computational biologists, biological chemists (particularly drug designers) and molecular bioengineers.

The book begins by introducing the basic principles of protein structure and function.... View Details

The Protein Power Lifeplan
by Michael R. Eades (Author), Mary Dan Eades (Author)

Introduces a lifestyle program that includes motivational advice, recipes, health tips, and nutritional guidelines to assist in treating major health problems, including diabetes, obesity, hypertension, and heart disease View Details

Power Vegan Meals: High-Protein Plant-Based Recipes for a Stronger, Healthier You
by Maya Sozer (Author)

High-Protein Vegan Meals for a High-Powered Lifestyle

In Power Vegan Meals, Maya creates easy meals that are high in protein and flavor and low in prep time, so they’re great for athletes as well as healthy, active people.

Drawing inspiration from international cuisine and comfort food favorites, Maya has crafted
over 75 diverse and flavorful gluten-free, soy-free, dairy-free and plant-based recipes that will keep you energized throughout the day. Recipes range from BBQ Jackfruit with Red Cabbage Slaw and guilt-free Peanut Butter Chocolate Fudge Bites to... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

The Consequences Of Racism
What does it mean to be judged before you walk through the door? What are the consequences? This week, TED speakers delve into the ways racism impacts our lives, from education, to health, to safety. Guests include poet and writer Clint Smith, writer and activist Miriam Zoila Pérez, educator Dena Simmons, and former prosecutor Adam Foss.
Now Playing: Science for the People

#465 How The Nose Knows
We've all got a nose but how does it work? Why do we like some smells and not others, and why can we all agree that some smells are good and some smells are bad, while others are dependant on personal or cultural preferences? We speak with Asifa Majid, Professor of Language, Communication and Cultural Cognition at Radboud University, about the intersection of culture, language, and smell. And we level up on our olfactory neuroscience with University of Pennsylvania Professor Jay Gottfried.