New 3D picture of human membrane protein enables development of targeted anti-histamines without side-effects
The crystal structure of human Histamine H1 receptor with doxepin
An international team of scientists using Diamond Light Source, the UK’s national synchrotron facility, has successfully solved the complex 3D structure of the human Histamine H1 receptor protein. Published in the journal Nature this week, their discovery¹ opens the way for the development of ‘third generation’ anti-histamines, specific drugs effective against various allergies without causing adverse side-effects.
The team, comprising leading experts from the USA (The Scripps Research Institute in California), Japan (Kyoto University), and the UK (Imperial College London and Diamond), worked across three continents for 16 months on the project.
Professor So Iwata, David Blow Chair of Biophysics at Imperial College London, BBSRC Fellow and Director of the Membrane Protein Laboratory at Diamond², said: “It took a considerable team effort but we were finally able to elucidate the molecular structure of the Histamine H1 receptor protein and also see how it interacts with anti-histamines. This detailed structural information is a great starting point for exploring exactly how histamine triggers allergic reactions and how drugs act to prevent this reaction.”
H1 receptor protein is found in the cell membranes of various human tissues including airways, vascular and intestinal muscles, and the brain. It binds to histamine, an important function of the immune system, but in susceptible individuals this can cause allergic reactions such as hay fever, food and pet allergies. Anti-histamine drugs work because they prevent histamine attaching to H1 receptors.
Dr Simone Weyand, post-doctoral scientist at Imperial College London, who conducted much of the experimental work at Diamond, said: “First generation anti-histamines such as Doxepin are effective, but not very selective, and because of penetration across the blood-brain barrier, they can cause side effects including sedation, dry mouth and arrhythmia. By showing exactly how histamines bind to the H1 receptor at the molecular level, we can design and develop much more targeted treatments.”