TSRI Researchers Investigate an Enzyme Important for Nervous System Health New Map of Protein Helps Researchers Understand Cellular Transport
LA JOLLA, CA May 11, 2015 Scientists from The Scripps Research Institute (TSRI), working closely with researchers at the National Institutes of Health (NIH), have mapped out the structure of an important protein involved in cellular function and nervous system development.
The new structure provides crucial information for understanding how the protein binds to cellular components. It's also the first structure determined of any ligase in the tubulin tyrosine ligase-like (TTLL) family.
Scientists have been especially curious about the role of TTLLs because mutations in these proteins have been linked to a range of neurodegenerative diseases, including retinal dystrophy and the rare Joubert syndrome.
This protein is highly expressed in the nervous system and has an integral role in neuronal development, said Elizabeth Wilson-Kubalek, senior staff scientist in Professor Ron Milligan's laboratory at TSRI and co-first author of the new paper with Christopher Garnham and Annapurna Vemu of the NIH's National Institute of Neurological Disorders and Stroke (NINDS).
The new research was published online ahead of print by the journal Cell.
Cellular Highways
While previous research had shown that TTLL7 modifies microtubules (hollow tubes that transport cellular components and act as highways and scaffolding in the cell) by adding one or more molecules of the amino acid glutamate, exactly how has remained a mystery. The new study goes a long way to answering that question.
In the new study, the researchers saw for the first time how three positively charged regions of TTLL7 interact with the microtubule substrate. Most importantly, they found that the active site of TTLL7 is ideally positioned to contact the negatively charged beta-tail of beta-tubulin, one of the two protein building blocks of the microtubule polymer (alpha- and beta-tubulin). The alpha and beta tails that protrude from the microtubule surface are known sites for modification, which in turn, determine which motors and associated proteins will bind to the microtubule.
These findings add to the growing understanding of the tubulin code a phenomenon where TTLL7 and similar proteins add amino acids to microtubules and prompt them to fast-track certain proteins for transport.
It's like opening up new lanes of traffic, said Gabriel Lander, an assistant professor at TSRI and a co-author of the new study.
A Piece of a Bigger Puzzle
The researchers were able to solve the structure of TTLL7 by combining x-ray crystallography and electron microscopy (EM). The team at NIH, led by the paper's senior author Antonina Roll-Mecak, used x-ray beams to create an atomic structure of the crystallized TTLL7 protein. The team at TSRI then used electron microscopy, which pelts samples with high-energy electrons, to see what TTLL7 looks like when bound to a microtubule. The atomic structure from the NIH team could be fit into the lower-resolution 3D EM image reconstruction to identify the regions of the protein that interacted with the microtubule surface.
Merging two structural techniques and biochemistry led us to a more complete story, said Wilson-Kubalek. It's really exciting to see something no one has ever seen before.
Wilson-Kubalek compares the research to putting together a puzzle. With this new piece in place, the researchers can tackle new aspects of microtubule function and work toward applications in human health.
The take-home message is that this is the first time we've seen how this protein sits on the microtubule, and this is going to be of major importance down the road, Wilson-Kubalek added.
In addition to Wilson-Kubalek, Milligan, Garnham, Vemu, Lander and Roll-Mecak, authors of the study, Multivalent Microtubule Recognition by Tubulin Tyrosine Ligase-Like Family Glutamylases, were Ian Yu and Agnieszka Szyk of the NIH's NINDS. See http://www.cell.com/cell/abstract/S0092-8674(15)00376-1
This research was supported by the National Resource for Automated Molecular Microscopy (NIGMS P41 GM103310); a NINDS postdoctoral fellowship; the Damon Runyon Cancer Research Foundation (DFS-#07-13); the Pew Scholars program; the Searle Scholars program; the intramural program of the NINDS and National Heart, Lung and Blood Institute; and the NIH (grants DP2 EB020402, GM-052468 and GM095573).
About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the worlds largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 2,700 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists including two Nobel laureates work toward their next discoveries. The institutes graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
# # #
For information:
Office of Communications
Tel: 858-784-2666
Fax: 858-784-8136
press@scripps.edu
Most recent headlines
06/10/2025
France T l visions, France's leading broadcaster, has received the 2025 EBU ...
04/09/2025
Monumental Sports & Entertainment (MSE), in collaboration with Dalet, has been a...
30/08/2025
WASHINGTON The Federal Communications Commission has adopted its FY 2025 Regulatory Fees Order that establishes the regulatory fee rates for the broadcast stati...
29/08/2025
Australian Red Cross and SBS launch training to help workplaces in the fight aga...
29/08/2025
The National Film and Video Foundation (NFVF), an agency of the Department of Sp...
29/08/2025
L3Harris Technologies has concentrated decades of expertise across the entire enterprise to develop affordable and reliable best-of-breed solutions to rapidly c...
29/08/2025
BURBANK, Calif. The CW Network and the Pac-12 Conference have announced a new media rights deal that will extend their broadcast partnership beginning with the ...
29/08/2025
NEW YORK Gracenote has released a new analysis of its global video dataset showing that the number of FAST channels grew nearly 14% from Q1 2025 and 76% since 2...
29/08/2025
SAN JOSE, Calif. Harmonic has announced a series of improvements to its live sports streaming solution that the company said will improve fan engagement, protec...
29/08/2025
NEW YORK and LOS ANGELES Fox Corp. and YouTube TV last night announced a renewal of the full portfolio of Fox networks, including Fox News Channel, Fox Business...
29/08/2025
Budapest, Hungary, August 2025 - The integration of Microsoft Teams Rooms (MTR) with Lightware's Taurus universal matrix switchers delivers a new level of f...
29/08/2025
Frequency, the engine behind many of the world's best-known streaming television channels, today announced it will launch Studio Live, a next-generation uni...
29/08/2025
In an era when AI and cyber resilience are essential, Scality will mark the 10th anniversary of Scality Day on October 16, 2025 in Paris. This flagship global e...
29/08/2025
Disguise's In-House Creative and Technical Teams Pre-Visualised, Programmed and Delivered Content for the Experience, All Powered by EX 3+
Technology solu...
29/08/2025
Disguise will be demonstrating the latest workflows for TV, film and live events on a number of partner booths at the show
Disguise, the industry-leading tech...
29/08/2025
STOCKHOLM, Sweden Accedo will showcase Accedo Compose, its AI agent-powered modular orchestration layer that assists streaming providers in transitioning client...
29/08/2025
LOS ANGELES Cineverse has announced that it is working with Xperi to bring four of its streaming channels to automobiles for the first time as part of the DTS A...
29/08/2025
DALLAS & ATLANTA Gray Media has announced an agreement with the sports streaming service Victory+ to simulcast 17 Dallas Stars NHL games in 15 television market...
29/08/2025
NEW YORK AND CULVER CITY Comcast NBCUniversal and Amazon have announced new and extended distribution agreements that will expand the content available on their...
29/08/2025
FOOTHILL RANCH, Calif. RED Digital Cinema will feature its Cine-Broadcast Module supporting live broadcast workflows during IBC2025, Sept. 12-15, at the RAI Ams...
29/08/2025
29 Aug 2025
Kyivstar Rings Opening Bell at Nasdaq Marking Landmark Listing and ...
29/08/2025
More than half of all NFL games live on Sky for the first timeFriday 29 August 2025
Sky Sports has announced a new three-year deal with the NFL, extending its ...
29/08/2025
Back to All News
RIV4LRIES: The Trailer of the New Series With Samuele Carrino ...
29/08/2025
Get ready for an inspiring and emotional insight into the world of competitive Irish dancing with My Story: Tomi Champion of the World airing on RT 2 this monda...
29/08/2025
RT has today announced that David McCullagh is to be the new presenter of RT Radio 1's flagship Today programme, which airs every weekday at 10am, replaci...
28/08/2025
By Kristin Feeley, Director, Documentary Film & Artist Programs
If you want to tell untold stories, if you want to give voice to the voiceless, you've got ...
28/08/2025
Directed by Steven Bognar and Julia Reichert, Sundance Institute-supported Amer...
28/08/2025
Corridos have been a cornerstone of M sica Mexicana for generations, telling stories rooted in everyday life. Now, a new chapter is taking shape: motivational c...
28/08/2025
Los corridos han sido un pilar de la M sica Mexicana durante generaciones, contando historias enraizadas en la vida cotidiana. Ahora, un nuevo cap tulo est tom...
28/08/2025
Earlier this month, we promised our Verano Forever party would bring the heat, a...
28/08/2025
L3Harris will provide the Polish F-16V fleet with the Viper Shield electronic warfare system as part of an upgrade program....
28/08/2025
Bilbao, August 26, 2025 - AgileTV, an international television and video technol...
28/08/2025
Ken Wilkinson is an Emmy Awards nominated New York audio engineer who specialises in production sound mixing for film, commercial, episodic and documentary work...
28/08/2025
NEW YORK FuboTV today announced that it will launch Fubo Sports, a skinny bundle that focuses on sports with a subscription price of $56 monthly....
28/08/2025
NEVADA City, Calif. At IBC2025, Sept. 12-15 at the RAI Amsterdam, Telestream will debut its new Global Ingest strategy, introducing a next-generation ingest arc...
28/08/2025
Dr. Rhoda Bernard Releases Groundbreaking Debut Book on Accessible Arts Educatio...
28/08/2025
TAG Video Systems, the leader in software-based IP end-to-end workflow monitoring, deep probing, and real-time visualization, has named Oliver Gappa as Sales Di...
28/08/2025
AI-based voice enhancement will be among a series of innovations making their IBC 2025 debut on the DHD stand B46 in Hall 8 at the RAI Amsterdam Convention Cent...
28/08/2025
Telef nica Servicios Audiovisuales (TSA), the leading system integrator and service provider in the media sector in Spain, with the support of Appear, the globa...
28/08/2025
To fully immerse sailing fans in the world's biggest offshore yacht race, production company, Optical Media turned to LiveU's On-site Production solutio...
28/08/2025
Working with Calrec on its most recent overhaul, radio and television broadcaster, WNED has migrated to a fully IP infrastructure with multiple Type R consoles,...
28/08/2025
Cleeng, the Subscriber Retention Management (SRM ) inventor, has unveiled Cleeng Pro, the first-ever direct-to-consumer (D2C) subscription management platform t...
28/08/2025
Zixi, the industry leader in live broadcast-quality video over IP, today announced that French media distribution platform OKAST has selected Zixi to enable rel...
28/08/2025
Solution offers a streamlined, speaker-free architecture to optimize integration with premium external loudspeakers and advanced loudness metering
Nixer Pro Au...
28/08/2025
Cinegy, the premier provider of software-defined television technology, has announced a strategic partnership with Vision One Touch Film Production Services L.L...
28/08/2025
Telestream, a global leader in media workflow technologies, will debut its new Global Ingest strategy at IBC2025, introducing a next-generation ingest architect...
28/08/2025
Tier 1 operator selects Broadpeak to power high-performance, unified CDN solution across Norway, Sweden and Finland
Broadpeak, a leader in streaming and moneti...
28/08/2025
Leading video software provider, Synamedia, today announced that 24 Frames Digital, one of India's leading live event streaming service providers, has chose...
28/08/2025
Meet VisualOn at IBC2025: See What's Next in AI-Powered Video Streaming Join VisualOn at IBC2025 and discover how our AI-driven Optimizer and advanced media...
TSRI Researchers Investigate an Enzyme Important for Nervous System Health New Map of Protein Helps Researchers Understand Cellular Transport
