Getting to the heart of heart beats: Cardiac thin filament structure and function revealed

January 09, 2020

Osaka, Japan - Researchers at Osaka University used electron cryomicroscopy (CryoEM) to image essential cardiac muscle components, known as thin filaments, with unprecedented resolution. They also discovered the mechanism by which these filaments regulate heart beat via cardiac muscle contractions in the presence or absence of calcium ions by changing their conformations. This work may have application in the development of new drugs for treating heart conditions caused by mutations that affect these structures and functions.

The human heart is a remarkable organ, capable of pumping blood for a lifetime without rest. However, many of the details of its inner workings remain unknown, partly because the exact structures of its muscle proteins in their natural forms are difficult to image. This is especially true for "thin filaments" - tiny filamentous structures made up of proteins called actin, troponin, and tropomyosin - owing to their complex interactions and small size. It has long been known that cardiac muscle contraction is controlled by the repeated increase and decrease in the concentration of calcium ions within muscle cells and that the control of contraction is accomplished by changes in the structure of the thin filaments when these ions bind to them. However, the exact mechanism was unclear.

Now, by using CryoEM, a technique recognized with the 2017 Nobel Prize in Chemistry, researchers at Osaka University have revealed the highest-resolution structural images of these proteins to date. Conventional electron microscopy usually damages fragile biological samples, meaning that their native shape in the body cannot be determined. In contrast, by the cryoEM technique, samples are flash-frozen so that proteins can be imaged while still in their native conformations.

"It has been very difficult to reveal the entire structure of the thin filament, but we succeeded in solving its structure using cryoEM and advanced image analysis," says first author Yurika Yamada. The Osaka team demonstrated how, in the absence of calcium ions, myosin access to the actin regions are blocked so that myosin heads cannot attach to them for muscle contraction. However, the binding of calcium ion changes the conformation of the thin filaments, exposing the attachment sites for contraction.

"Since many mutations in the component proteins of the thin filament are known to cause heart disease, including cardiac hypertrophy and cardiomyopathy, the revealed structures could provide a molecular and structural basis for novel drug design," explain senior authors Takashi Fujii and Keiichi Namba.

This research also highlights the power of cryoEM to reveal previously unseen anatomical detail with potential for yet unimagined medical breakthroughs.
-end-
This article, "Cardiac muscle thin filament structures reveal calcium regulatory mechanism," was published in Nature Communications at DOI: https://doi.org/10.1038/s41467-019-14008-1.

About Osaka University

Osaka University was founded in 1931 as one of the seven imperial universities of Japan and now has expanded to one of Japan's leading comprehensive universities. The University has now embarked on open research revolution from a position as Japan's most innovative university and among the most innovative institutions in the world according to Reuters 2015 Top 100 Innovative Universities and the Nature Index Innovation 2017. The university's ability to innovate from the stage of fundamental research through the creation of useful technology with economic impact stems from its broad disciplinary spectrum.

Website: https://resou.osaka-u.ac.jp/en/top

Osaka University

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.