Navigation Links
A firm molecular handshake needed for hearing and balance

Researchers have mapped the precise 3-D atomic structure of a thin protein filament critical for cells in the inner ear and calculated the force necessary to pull it apart.

In a study to be published November 7 in the journal Nature, a group led by David Corey, HMS professor of neurobiology, and Rachelle Gaudet, professor of molecular and cellular biology in the Faculty of Arts and Sciences at Harvard University, revealed the characteristics of the most vulnerable area of a structure called the tip link. Their findings open avenues for research in fields related to noise-induced hearing loss and certain genetic diseases.

"Tip links are absolutely vital to hair cells, and hair cells are absolutely vital for hearing and balance," said Corey. "We now have this new understanding of how noise can break a tip link and potentially cause a hearing problem."

The sensations of hearing and balance rely on hair cells, a family of cells located in the inner ear. Crucial to their function are tip links, strings of protein that physically connect the cilia or "hairs" found on these cells. When the cilia move in response to sensory stimuli head movement or the vibration of sound, for exampletension is applied to the tip links, which begins a process that ultimately sends nerve impulses to the brain.

Tip links are composed of two different types of proteins called cadherins, which connect in the middle to make one long string. Mutations in these proteins often result in congenital deafness and balance disorders. Scientists have only recently made strides toward understanding the nature of these cadherins, especially at their connection to each otherhypothesized to be the first area to break under stress.

To test this, Marcos Sotomayor, first author on the paper and a postdoctoral researcher in the lab of David Corey, investigated the structure of that bond.

He first synthesized and purified a large amount of the very ends of the proteins, where they connect. After crystallizing the purified proteins bound to each other, the team took advantage of powerful X-rays generated by a 3000-foot long electron accelerator at Argonne National Laboratory.

When X-ray light passes through a highly ordered crystal, it creates a regular diffraction pattern that can be used to reveal the structure of the proteins forming the crystal.

Sotomayor analyzed the diffraction pattern generated at Argonne and coupled it with biochemical data. From this, he created a complete 3-D map of the structure of bonded region, down to the position of each individual atom.

The map revealed that the two different cadherins bonded like two hands gripping each other's wrists. This molecular handshake was not mediated by calcium ions, as had been hypothesized, but it showed an intimate and extended interface not seen before in cadherin-cadherin bonding.

With this precise 3-D structure, the team used supercomputers to simulate the dynamics of these proteins under a variety of conditions, including applying forces to pull the bond apart. They found that it takes only half as much force to break the connection as it does to unfold the cadherins themselvesconfirming that the bond is indeed the weakest region of the tip link. They suggest the tip link is strong enough to withstand normal sound, but the connection is likely the first to break under loud noises.

They also showed how certain mutations that produce deafness could weaken the bond, perhaps allowing it to come apart even with quiet sound.

The group plans to characterize tip-link structure further, moving on to other parts such as where the cadherins link to tension-activated ion channels at the tips of the hair cells' cilia.

Contact: David Cameron
Harvard Medical School

Related biology technology :

1. USC Center For Applied Molecular Medicine To Honor Sumner Redstone And Murray Gell-Mann, Ph.D. At The Inaugural REBELS WITH A CAUSE Gala
2. Merrimack Pharmaceuticals To Present Preliminary Clinical Data For Novel Therapies Targeting Molecular Pathways In Advanced Cancers
3. Indian Pharma MNC Piramal Investing in German Molecular Imaging Technology
4. Spectrometry Market (Atomic, Molecular and Mass Spectrometry) - Global Scenario, Trends, Industry Analysis, Size, Share & Forecast 2011 - 2017
5. Spectrometry Industry (Atomic, Molecular and Mass Spectrometry) is Expected to Reach USD 15.2 Billion Globally in 2017: Transparency Market Research
6. IMDx Obtains CE-Marking for an Automated Molecular Test for Detection and Differentiation of Herpes Simplex Viruses 1 and 2
7. Sifting liquid at the molecular level
8. Neogen launches the fastest molecular pathogen test
9. Strange cousins: Molecular alternatives to DNA, RNA offer new insight into lifes origins
10. GenScript Rush Gene Synthesis - Driving Molecular Biology Research Faster
11. Molecular graphene heralds new era of designer electrons
Post Your Comments:
(Date:6/27/2016)... ... June 27, 2016 , ... Newly created 4Sight Medical ... to the healthcare market. The company's primary focus is on new product introductions, ... strategies that are necessary to help companies efficiently bring their products to market. ...
(Date:6/24/2016)... 24, 2016 Epic Sciences unveiled a ... susceptible to PARP inhibitors by targeting homologous recombination ... The new test has already been incorporated into ... cancer types. Over 230 clinical trials ... pathways, including PARP, ATM, ATR, DNA-PK and WEE-1. ...
(Date:6/23/2016)... Mass. , June 23, 2016   ... development of novel compounds designed to target cancer ... napabucasin, has been granted Orphan Drug Designation from ... the treatment of gastric cancer, including gastroesophageal junction ... stemness inhibitor designed to inhibit cancer stemness pathways ...
(Date:6/23/2016)... Calif. , June 23, 2016  The Prostate Cancer Foundation ... increasingly precise treatments and faster cures for prostate cancer. Members of the Class ... across 15 countries. Read More About the Class of ... ... ...
Breaking Biology Technology:
(Date:4/13/2016)... , April 13, 2016  IMPOWER physicians supporting Medicaid ... setting a new clinical standard in telehealth thanks to ... leveraging the higi platform, IMPOWER patients can routinely track ... and body mass index, and, when they opt in, ... convenient visit to a local retail location at no ...
(Date:3/29/2016)... BOCA RATON, Florida , March 29, 2016 /PRNewswire/ ... ("LegacyXChange" or the "Company") LegacyXChange "LEGX" and SelectaDNA/CSI Protect ... Synthetic DNA in ink used in a variety of ... preventing theft. Buyers of originally created collectibles from athletes ... authenticity through forensic analysis of the DNA. ...
(Date:3/22/2016)... OTTAWA, Ontario , PROVO ... 2016 Newborn Screening Ontario (NSO), which operates ... for molecular testing, and Tute Genomics and ... process management technology respectively, today announced the launch of ... new next-generation sequencing (NGS) testing panel. ...
Breaking Biology News(10 mins):