Breaking News
December 15, 2018 - Gut bacteria may modify effectiveness of anti-diabetes drugs
December 15, 2018 - How imaginary friends could boost children’s development
December 15, 2018 - Study provides new insights into molecular mechanisms underlying role of amyloid in Alzheimer’s disease
December 15, 2018 - For the asking, a check is in the mail to help pay for costly drugs
December 15, 2018 - UA scientists uncover biological processes leading to rare brain disorder in babies
December 15, 2018 - The largest database on industrial poisons
December 15, 2018 - ESMO Immuno-Oncology Congress showcases novel technologies set to benefit many cancer patients
December 15, 2018 - Ovid Therapeutics Announces Plans to Move into a Phase 3 Trial in Pediatric Patients Based on End-of-Phase 2 Meeting for OV101 in Angelman Syndrome
December 15, 2018 - Left ventricular noncompaction – Genetics Home Reference
December 15, 2018 - Children’s sleep not significantly affected by screen time, new study finds
December 15, 2018 - When should dementia patients stop driving? A new guidance for clinicians
December 15, 2018 - Researchers use INTEGRA’s VIAFLO 96/384 to streamline the experimental workflow
December 15, 2018 - Researchers discover protein involved in nematode stress response
December 15, 2018 - Cancer patients have greater risk of developing shingles, study shows
December 14, 2018 - UAlberta scientists identify biomarkers for detecting Alzheimer’s disease in saliva samples
December 14, 2018 - Study uncovers link between tube travel and spread of flu-like illnesses
December 14, 2018 - Caffeine plus another compound in coffee may fight Parkinson’s disease
December 14, 2018 - GW researchers review studies on treatments for prurigo nodularis
December 14, 2018 - Lack of peds preventive care ups unplanned hospital admissions
December 14, 2018 - Miscarriage: When Language Deepens Pain
December 14, 2018 - New method helps better understand pathological development of ALS
December 14, 2018 - Intellectually active lifestyle confers protection against neurodegeneration in Huntington’s patients
December 14, 2018 - Mammalian collagen nanofibrils become stronger and tougher with exercise
December 14, 2018 - Considerable Morbidity, Mortality Due to Animal Encounters
December 14, 2018 - Researchers find inhibiting one protein destroys toxic clumps seen in Parkinson’s disease
December 14, 2018 - How early physical therapy can lessen the long-term need for opioids
December 14, 2018 - Depression, suicide rates highest in Mountain West states
December 14, 2018 - New model could cure the potential to underestimate how quickly diseases spread
December 14, 2018 - Exercise-induced hormone activates cells critical for bone remodeling in mice
December 14, 2018 - Researchers discover new mechanism behind spread of malignant pleural mesothelioma
December 14, 2018 - Health Tip: Celebrate a Healthier Holiday
December 14, 2018 - Scalpel-free surgery enhances quality of life for Parkinson’s patients, study finds
December 14, 2018 - Early physical therapy can reduce risk, amount of long-term opioid use | News Center
December 14, 2018 - Genetic marker, predictor of early relapse in common childhood cancer discovered
December 14, 2018 - Study could lead to a potential new way of treating sepsis
December 14, 2018 - New protein complex helps embryonic stem cells to maintain their indefinite potential
December 14, 2018 - Salk professor receives $1.8 million from NOMIS Foundation for research on mechanisms to promote health
December 14, 2018 - New discovery will improve the safety and predictability of CRISPR
December 14, 2018 - Geneticists discover how sex-linked disorders arise
December 14, 2018 - New method to visualize small-molecule interactions inside cells
December 14, 2018 - Study describes mechanism that makes people more vulnerable to hunger-causing stimuli
December 14, 2018 - Chronic opioid therapy associated with increased healthcare spending and hospital stays
December 14, 2018 - Blood Types
December 14, 2018 - Obesity linked to increased risk of early-onset colorectal cancer
December 14, 2018 - Blood test helps identify distinct molecular signatures in children with cystic fibrosis
December 14, 2018 - In California, doctors accused of sexual misconduct often get second chances
December 14, 2018 - Scientists use water to track electrical activity of nerve cells
December 14, 2018 - Recurrence of urinary tract infection may depend on bacterial strain, study shows
December 14, 2018 - GBT Announces U.S. FDA Agrees with its Proposal Relating to Accelerated Approval Pathway for Voxelotor for the Treatment of Sickle Cell Disease and GBT Plans to Submit New Drug Application (NDA)
December 14, 2018 - Partial Thromboplastin Time (PTT) Test: MedlinePlus Lab Test Information
December 14, 2018 - Common tactics for health promotion at work may be detrimental to employees with obesity
December 14, 2018 - Myths about migration and health not supported by available evidence
December 14, 2018 - Recent findings on rare genetic disorder may help develop new treatment options
December 14, 2018 - New drug shows promise in treating sarcomas
December 14, 2018 - Scientists perform lung lavage as new approach for tuberculosis diagnosis in rhinoceros
December 14, 2018 - Answering the Biggest Neurological Research Questions of Today
December 14, 2018 - Recent winners of the Nobel Medicine Prize
December 14, 2018 - KHN’s ‘What the Health?’ Insurance enrollment is lagging — and there are lots of reasons why
December 14, 2018 - Study assesses safety and efficacy of new treatment for pancreatic cancer
December 14, 2018 - Weakened metabolism of immune T cells may account for serious complications in elderly
December 14, 2018 - Study finds drug targets for Ebola, Dengue, and Zika viruses
December 14, 2018 - Face masks may offer protection against staph bacteria for hog farm workers and their household members
December 14, 2018 - Shining new light on neuron firing
December 14, 2018 - Study highlights need for personalized approach to treat ICU acquired delirium
December 14, 2018 - Soot particles from road traffic significantly contribute to air pollution
December 14, 2018 - Massage helps relieve pain, improve mobility in patients with knee osteoarthritis
December 14, 2018 - Researchers explore home healthcare nurses’ knowledge attitudes toward infection control
December 14, 2018 - Average outpatient visit in the U.S. costs nearly $500, shows new study
December 14, 2018 - Reference Infliximab, Biosimilar Equivalent for Crohn’s Disease
December 14, 2018 - New contact lens to treat eye injuries
December 14, 2018 - Acne could have a genetic basis find researchers promising new cure
December 14, 2018 - Higher physical activity associated with improved mood
December 14, 2018 - New UGA study points to optimal hypertension treatment for stroke patients
December 14, 2018 - Study highlights factors that can reduce food cravings
December 14, 2018 - Researchers discover Ebola-fighting protein in human cells
December 14, 2018 - Fentanyl surpasses heroin in cause of U.S. drug overdose deaths
December 14, 2018 - When Heart Attack Strikes, Women Often Hesitate to Call for Help
December 14, 2018 - A warning about costume contacts
December 14, 2018 - Study examines link between peripheral artery disease and heart attack
December 14, 2018 - Researchers develop biotechnological tool to produce antifungal proteins in plants
CNIO researchers determine structure of protein complex related to cell survival

CNIO researchers determine structure of protein complex related to cell survival

image_pdfDownload PDFimage_print

A team from the Spanish National Cancer Research Centre (CNIO) has determined for the first time the high-resolution structure of a complex (R2TP) involved in key processes for cell survival and in diseases such as cancer. This achievement has been made possible by using high-resolution cryo-electron microscopy, a technique brought to the CNIO thanks to Óscar Llorca, director of the Structural Biology Programme and lead author on the paper published in Nature Communications.

In 2017, the Nobel Prize for Chemistry was awarded to three scientists (Jacques Dubochet, Joachim Frank, and Richard Henderson) for their work on the development of cryo-electron microscopy. This technique can capture images of individual molecules, which are used to determine their structure and to ascertain biological processes in atomic detail.

Óscar Llorca and his team have used this technique to learn about the structure and functioning of a complex system called R2TP, which is involved in various key processes for cell survival such as the activation of the kinases mTOR, ATR and ATM, proteins that are the target of various cancer drugs currently being developed.

This work is the result of a collaborative project with the research group led by Professor Laurence H. Pearl at Sussex University in the UK, and has also involved the CSIC Centre for Biological Research (CIB), CIC bioGUNE, and the Laboratory of Molecular Biology in Cambridge, UK.

Complex and versatile ‘assembly machinery’

mTOR, ATR and other related kinases do not work in isolation but rather by interacting and forming complexes with other proteins, which are essential for their normal functioning. The assembly of these structures with multiple components does not take place in cells spontaneously. The R2TP system and the HSP90 chaperone are crucial for the assembly and activation of mTOR and other related kinases, but how this happens in cells is still somewhat of a mystery. “If we understand this assembly pathway – explains the researcher – we will be able to identify new ways of targeting the activity of these kinases”.

Thanks to cryo-electron microscopy, “we have been able to visualise, for the first time, the high-resolution structure of the human R2TP system”, states Llorca. What has most surprised the researchers is the unexpected complexity of the human R2TP system, compared to its yeast homologues. The microscope images show that R2TP is a large platform capable of putting HSP90 in contact with the kinases on which HSP90 must act. When viewed under the microscope, R2TP looks like a jellyfish with three very flexible ‘tentacles’ made up of RPAP3 protein. The kinases of the mTOR family are recruited to the base of this jellyfish’s ‘head’, while HSP90 is hooked by the tentacles and taken to the kinases, thanks to their flexibility.

“This first observation of the human R2TP system has allowed us to understand its structure and functioning mechanisms, which were previously unknown. Our next steps will be to study the details of how R2TP and HSP90 are able to assemble the complexes made up of kinases of the mTOR family, in order to find ways of interfering with these processes”, concludes Llorca. “The R2TP system is also involved in the activation of other essential molecules for the cell and in the development of cancer, such as the RNA polymerase, telomerase, or the ‘splicing’ system, areas that we intend to explore in the future”.

Source:

https://www.cnio.es/ing/publicaciones/structure-of-a-protein-complex-related-with-cell-survival-revealed

Tagged with:

About author

Related Articles