{"id":48489,"date":"2025-02-12T10:05:52","date_gmt":"2025-02-12T15:05:52","guid":{"rendered":"https:\/\/engineering.jhu.edu\/materials\/?post_type=news&p=48489"},"modified":"2025-02-28T16:31:37","modified_gmt":"2025-02-28T21:31:37","slug":"brain-power-activated","status":"publish","type":"news","link":"https:\/\/engineering.jhu.edu\/materials\/news\/brain-power-activated\/","title":{"rendered":"Brain Power, Activated"},"content":{"rendered":"

A team that included Johns Hopkins materials scientists has uncovered new insights into the structure of TrkB, an important protein that helps brain cells grow and adapt.\u00a0<\/span>\u00a0<\/span><\/p>\n

Their work, which appears in <\/span>Nature Communications<\/i><\/span><\/a>, could help scientists develop more effective drugs for conditions ranging from depression and post-traumatic stress disorder (PTSD) to cancer.<\/span>\u00a0<\/span><\/p>\n

\u201cWe already knew that TrkB is a protein found in cell membranes in the brain that aid with cell growth and function, and when it’s working, it dimerizes \u2013 coming together and forming pairs,\u201d <\/span>s<\/span>ays team member Daniel McKenzie, a doctoral student in the Whiting School of Engineering\u2019s <\/span>Department of Materials Science and Engineering<\/span><\/a>. \u201cOur research discovered that a specific part of TrkB, the transmembrane helix, plays a key role in turning it on.\u201d<\/span>\u00a0<\/span><\/p>\n

Researchers studied the interactions of TrkB with fluoxetine, also known as Prozac, because it binds to the transmembrane helix of TrkB.\u00a0<\/span>\u00a0<\/span><\/p>\n

“We found that when fluoxetine attaches to TrkB, the protein is in its \u201cactive\u201d state, indicating that it could start a chain of reactions in the brain to possibly treat mental health conditions,\u201d says McKenzie.<\/span>\u00a0<\/span><\/p>\n

Based on their previous knowledge about the protein, McKenzie and adviser <\/span>Kalina Hristova<\/span><\/a>, a professor of materials science and engineering and core researcher at Johns Hopkins <\/span>Institute for NanoBioTechnology,<\/span><\/a> and collaborators from Italy, Spain, and Russia, aimed to investigate receptor interactions to better understand how TrkB functions when it binds to antidepressants.<\/span>\u00a0<\/span><\/p>\n

McKenzie and Hristova\u2019s portion of the study builds on investigations by team member Konstantin S. Mineev, a principal investigator at the <\/span>Shemyakin and Ovchinnikov <\/span>Institute of Bioorganic Chemistry in Russia, who used nuclear magnetic resonance (NMR) spectroscopy to identify eight key amino acids in TrkB\u2019s transmembrane helix dimer that appear crucial for dimerization. Also foundational to the work was Mar\u00e7al Vilar, a principal investigator at the <\/span>Valencia Biomedical Research Foundation in Spain,<\/span> whose team confirmed these amino acids\u2019 importance by showing that individual mutations at these sites impaired the receptor\u2019s response. If a mutated TrkB did not work as well as the normal one, researchers inferred that the amino acid was important for its function.<\/span>\u00a0<\/span><\/p>\n

\u201cOne amino acid, serine, was found to be important because when it was mutated at position 441, TrkB\u2019s activity appeared to decrease or stop completely,\u201d says McKenzie. \u201cWe used a technique called number and brightness to investigate this phenomenon further and found that the mutation didn\u2019t stop TrkB from dimerizing \u2013 it was in an inactive state but still formed pairs.\u201d<\/span>\u00a0<\/span><\/p>\n

Typically, the activation of the receptor and the dimerization are processes that are linked. A mutation that prevents activation but still allows the receptors to pair up is unusual and presents new research possibilities, the investigators say.<\/span>\u00a0<\/span><\/p>\n

\u201cA single amino acid out of 800 inactivating the receptor is quite rare, especially because it is located in the transmembrane domain which is largely considered to be unimportant for signaling,\u201d says McKenzie.<\/span>\u00a0<\/span><\/p>\n

The team\u2019s next step is to test TrkB\u2019s response to other antidepressant medications and psychoactive substances, like LSD, to hopefully understand how the functions of TrkB is affected by antidepressants. Scientists are still uncertain if TrkB can be a target of other medications to treat mental health challenges.<\/span>\u00a0<\/span><\/p>\n

\u00a0\u201cThese are difficult questions to tackle, and we will continue working with structural biologists and biochemists to move forward,\u201d says Hristova.<\/span>\u00a0<\/span><\/p>\n

This study<\/span> was led by researchers from Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, CNR Neuroscience Institute, and the Valencia Biomedical Research Foundation.<\/span>\u00a0<\/span><\/p>\n","protected":false},"template":"","class_list":["post-48489","news","type-news","status-publish","hentry","news_categories-research"],"acf":[],"yoast_head":"\nBrain Power, Activated - Department of Materials Science & Engineering<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/engineering.jhu.edu\/materials\/news\/brain-power-activated\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Brain Power, Activated - Department of Materials Science & Engineering\" \/>\n<meta property=\"og:description\" content=\"A team that included Johns Hopkins materials scientists has uncovered new insights into the structure of TrkB, an important protein that helps brain cells grow and adapt.\u00a0\u00a0 Their work, which…\" \/>\n<meta property=\"og:url\" content=\"https:\/\/engineering.jhu.edu\/materials\/news\/brain-power-activated\/\" \/>\n<meta property=\"og:site_name\" content=\"Department of Materials Science & Engineering\" \/>\n<meta property=\"article:modified_time\" content=\"2025-02-28T21:31:37+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"3 minutes\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Brain Power, Activated - 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