TSRI Study Points to Unexplored Realm of Protein Biology, Drug Targets LA JOLLA, CA June 18, 2015 Scientists at The Scripps Research Institute (TSRI) have devised a powerful set of chemical methods for exploring the biology of proteins.
The techniques are designed to reveal protein interactions with lipids a class of biological molecules including some vitamins (A, D, E), hormones (estrogen, testosterone), neurotransmitters (endocannabinoids) and components of fat (triglycerides, cholesterol).
It has long been clear that lipids are important in biology, but it has been challenging to achieve a global portrait of how they interact with proteins, said senior investigator Benjamin F. Cravatt, who chairs TSRI's Department of Chemical Physiology. This approach allows us not only to identify lipid-interacting proteins but also to discover small molecules or ligands' that selectively block these lipid-protein interactions, helping us to study their functions.
In some cases, such ligands could become the basis for new drugs. In fact, initial surveys by Cravatt's team revealed a surprisingly large number of lipid-protein interactions and while some of these interactions are already targeted by existing drugs, most are not.
Traditionally, scientists have theorized fairly narrow limits on which proteins can be targeted with small-molecule ligands, but our results suggest that those boundaries are much wider, said Cravatt.
The team's findings were reported in the journal Cell on June 18, 2015.
Surprising Results
The study, whose co-first authors were Micah Niphakis, who at the time was a postdoctoral fellow in the Cravatt laboratory, and graduate student Kenneth M. Lum, emerged from an effort to discover protein-binding partners of arachidonoyl lipids, which are involved in many physiological responses such as pain, inflammation, mood and appetite.
Niphakis began by making probe molecules that mimic the structure of arachidonoyl lipids and capture protein-binding partners when exposed to ultraviolet light. He found that each of the probes fastened to hundreds of distinct proteins in human and mouse cells. Probes mimicking other lipids also revealed large sets of protein interactions.
A big challenge in using the lipid probes was to determine which protein interactions were likely to be selective and biologically relevant and not just random, weak bindings. One way we addressed that challenge was to use multiple, structurally distinct probes to look at the differences in how they bound to a given protein, said Niphakis.
As Niphakis and his colleagues worked with the probes, they found they could quickly generate extensive maps of a given lipid's protein-binding partners and, in many cases, even map the region of the protein that the lipid probes bound information that could be put to multiple uses.
Profiling Drug Compounds
One was to profile the activities of any drug compound, essentially by comparing how lipid-protein interaction maps change in the presence of the drug. Such changes would be due largely to the drug's interference with lipid-protein binding events. The team found that, while some drugs they tested this way were highly selective in the sense that they bound only to their intended protein targets, others showed evidence of strong bindings to additional, off-target proteins which could produce their own biological effects.
Similarly, the TSRI researchers used their lipid probes to make a high-throughput screening assay to discover ligands that bind to proteins at their lipid interaction sites. In one case, the researchers screened a small-molecule compound library and identified compounds that bind tightly to NUCB1, an otherwise little-known protein that showed strong interactions with the arachidonoyl probes. The researchers then employed these ligand compounds to study NUCB1's functions in detail, showing, for example, that it facilitates the breakdown of endocannabinoids and related lipids, perhaps by acting as a transporter.
The Cravatt laboratory is now using the same approach to study the functions of other proteins in their lipid interaction maps.
There are a lot of proteins in our dataset that haven't been characterized, yet have strong interactions with our lipid probes, said Cravatt.
In principle, a similar approach could be used to discover and study protein interactions with other, non-lipid types of biomolecules. Alternative probes would be valuable for surveying other types of metabolite-protein interactions, said Niphakis.
In addition to Cravatt, Niphakis and Lum, contributors to the paper, A global map of lipid-binding proteins and their ligandability in cells, were Armand B. Cognetta III, Bruno E. Correia, Taka-Aki Ichu, Jose Olucha, Steven J. Brown, Soumajit Kundu, Fabiana Piscitelli and Hugh Rosen, all of TSRI.
Funding was provided by the National Institutes of Health (CA132630, DA032541).
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
Most recent headlines
11/12/2025
Dalet, a leading provider of cloud-native, end-to-end media workflow solutions, ...
06/12/2025
In a live broadcast from the Reagan National Defense Forum, L3Harris Chair and CEO Christopher Kubasik joined Morgan Brennan on CNBCs Closing Bell: Overtime. Ku...
06/12/2025
FORT LAUDERDALE, Fla. A new survey from Pixitmedia by Datacore revealed a major shift in the Media & Entertainment industry in media archiving, with 85% of resp...
06/12/2025
HACKENSACK, N.J. LiveU has announced that the national public broadcaster Czech Television has completed one of the largest LiveU live production deployments fo...
06/12/2025
NEW YORK The National Academy of Television Arts and Sciences (NATAS) presented the Excellence in Production Technology Emmy Award to NASA+ and Dr. Tom Leight...
05/12/2025
2025 Sports Broadcasting Hall of Fame: Curt Gowdy Jr. - Master Storyteller, Nati...
05/12/2025
SVG Sit-Down: Veritone's Sean King on the Power of Mining Video, Audio DataThe company's Data Refinery offers users total control and governance over da...
05/12/2025
Platinum White Paper: Inside the Nashville Predators' Unified, Flexible, Sca...
05/12/2025
Netflix Reaches Agreement To Acquire Warner Bros. Following Planned WBD SplitThe deal does not include WBDs sports assets like TNT Sports (US, UK, LatAm), Euros...
05/12/2025
FOX Sports Returns to Indianapolis for Primetime Broadcast of Big Ten Championsh...
05/12/2025
SVG Summit 2025 Preview: Digital Engagement & Monetization Workshop Tackles the ...
05/12/2025
Atlanta United Lights Up New Emory Healthcare Studio With First Live Broadcast f...
05/12/2025
As Messi Takes the Pitch, MLS, Apple, NEP Roll Out Largest MLS Cup Production Ev...
05/12/2025
ESPN Enters College Football's Most Intense Month With Elevated Workflows fo...
05/12/2025
It's about that time! Awards season is in full swing, and the Film Independe...
05/12/2025
Every year, Spotify Wrapped offers a personalized look back at the audio that defined your year. It's a snapshot of your listening habits, designed to tell ...
05/12/2025
In 2025, Spotify's EQUAL, GLOW, and RADAR programs celebrated women, LGBTQIA , and emerging artists who turned moments into milestones. From breaking record...
05/12/2025
In our latest blog, we explain how Wi-Fi 7 rollouts can drive consumer loyalty with value-add services such as consumer cybersecurity. We also explore how this ...
05/12/2025
LOS ANGELES Netflix announced it has entered into an agreement to acquire the assets of Warner Bros. for $82.7 billion....
05/12/2025
NEW YORK Nielsens Gracenote has launched Gracenote Content Connect, a new ad platform that provides agencies, brands, supply-side platforms (SSPs) and demand-si...
05/12/2025
NEW YORK In an most important update to the workings of deal-based programmatic advertising, IAB Tech Lab has released version 1.0 of its Deals API for public c...
05/12/2025
NEW YORK Pass the turkey. Pass the stuffing. Pass the cranberry sauce. All are common requests of Americans celebrating Thanksgiving Day with family and f...
05/12/2025
NEW YORK Iris, the new cloud-connected camera control platform, has officially launched with features that turn virtually any PTZ camera into a software-connect...
05/12/2025
HOLLYWOOD, Calif. Netflix announced today that it has entered into an agreement to acquire the assets of Warner Bros. for $82.7 billion....
05/12/2025
NEW YORK Iris, the new cloud-connected camera control platform, has officially launched with features that turn virtually any PTZ camera into a software-connect...
05/12/2025
WASHINGTON The Federal Communications Commission has approved AT&T's $1.02 billion acquisition of spectrum from UScellular in a decision that was issued sho...
05/12/2025
The Best Coldplay Songs: 21 Tracks That Shoot for the Stars From Yellow to Viva La Vida, Fix You to Paradise, this playlist goes back to the start.
December ...
05/12/2025
Zafris Lecture Series Brings Nabil Ayers to Berklee The 32nd annual James G. Zafris Distinguished Lecture series was held on Thursday, November 13, with guest...
05/12/2025
Introducing New Perks to Help You Get Even More from LinkedIn Premium Published on Dec 5, 2025 Categories: Company News, Product News
LinkedIn Corporate Co...
05/12/2025
Friday 5 December 2025
A new Game of Thrones Tale: Official trailer for Sky Exc...
05/12/2025
Back to All News
Don Lee, Lee Jin-uk, and Lalisa Manobal to Star in Netflix Act...
05/12/2025
Tis the season of giving once again and this year we've taken our Give Back Fridays' concept and turned it on its head.
In the autumn we were approach...
05/12/2025
Brayden Gogis doesn't remember a time when he wasn't completely fixated on games in all forms. In preschool, when they asked us to dress up as what we ...
05/12/2025
The Grinch steals the spotlight as the theme for The Late Late Toy Show 2025
Tune in tonight at 9:35pm on RT One and worldwide on RT Player
#LateLateToyShow...
05/12/2025
RT Announces New Presenters of Flagship News Programmes
New RT Six One News co-presenter Tommy Meskill
Sarah McInerney & Justin McCarthy join Morning Ir...
04/12/2025
ToolsOnAir Blackmagic Design HyperDeck Event Presets for just:in mac pro 2025 & ...
04/12/2025
ToolsOnAir AJA Ki Pro Event Presets for just:in mac pro 2025 & just:in linux
More Details:Starting with version 5.5, both just:in mac pro and just:in linux sol...
04/12/2025
Wangu Kanuri from Kenya and Godwin Asediba from Ghana are two of this years finalists for Thomsons Young Journalist of the Year Award. The pair are runners-up i...
04/12/2025
SVG Sit-Down: ProximaVision's Claudio Lisman on Why Tethered Drones Could Be...
04/12/2025
SVG Campus Shot Callers: Imry Halevi, Senior Associate Director of Athletics, Co...
04/12/2025
Platinum White Paper: LiveU Lightweight Sports Production: A Step Change in Spor...
04/12/2025
London to Riyadh: DAZN brings the boxing glamour to new production levels for Be...
04/12/2025
Analysis: Paramount bets on the battering ram' with Champions League play By Callum McCarthy, Editor-at-Large
Tuesday, December 2, 2025 - 10:12
Print ...
04/12/2025
Space City Home Network Launches SCHN DTC App for Astros and RocketsThe Rockets and Astros were previously the lone NBA and MLB teams without a DTC appBy Jason...
04/12/2025
SVG Summit 2025 Preview: Content Workflows Workshop Spotlights Evolution of Spor...
04/12/2025
New Sponsor Spotlight: Geotech's Patrick Wambold On the Unreal Engine Revolu...
04/12/2025
Curt Gowdy Jr. - Master Storyteller, Nationally and RegionallyBy Jason Dachman, Editorial Director, U.S.
Thursday, December 4, 2025 - 1:52 pm
Print This Sto...
04/12/2025
(L-R) Rebecca Lichtenfeld, Mohammadreza Eyni, Sara Khaki, and Judith Helfand att...
04/12/2025
SBS launches Future Frames initiative to support emerging First Nations video ed...
TSRI Study Points to Unexplored Realm of Protein Biology, Drug Targets LA JOLLA, CA June 18, 2015 Scientists at The Scripps Research Institute (TSRI) have devised a powerful set of chemical methods for exploring the biology of proteins.
