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.
By showing exactly how histamines bind to the H1 receptor at the molecular level, we can design and develop much more targeted treatments.” The research was technically challenging because membrane proteins are notoriously difficult to crystallise – a step that is vital in solving protein structures using a synchrotron.
The proteins were grown in cells at Kyoto University in Japan, then processed cell material was flown to Professor Raymond Stevens at The Scripps Research Institute in La Jolla, California, who leads the GPCR Network of the National Institute of General Medical Sciences' Protein Structure Initiative, and has developed powerful techniques to analyse membrane proteins and crystallise G-protein coupled receptors (GPCRs) funded by the National Institutes of Health Common Fund.
Advances in structural biology have accelerated greatly as a result of access to the synchrotron facilities that have been developed around the world in the past 25 years.
Researchers in the UK are at the forefront of this work and Diamond Light Source provides cutting edge facilities for protein structure determination.
We’ve benefited from rapid-access to the beamline and round the clock support for our experiments and data analysis work.” Professor Gerd Materlik, Diamond’s Chief Executive, said: “Solving this challenging structure so quickly is a significant achievement for Profs Iwata and Stevens, their groups and the I24 beamline team.
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.BBSRC provides institute strategic research grants to the following: The Babraham Institute, Institute for Animal Health, Institute for Biological, Environmental and Rural Sciences (Aberystwyth University), Institute of Food Research, John Innes Centre, The Genome Analysis Centre, The Roslin Institute (University of Edinburgh) and Rothamsted Research.The Institutes conduct long-term, mission-oriented research using specialist facilities.Diamond currently has five experimental stations dedicated to structural biology as well as the on-site Membrane Protein Laboratory, recently developed in partnership with Imperial College London and funded by the Wellcome Trust.Since Diamond opened in 2007, over 500 protein structures have been solved there including enzymes associated with hypertension, tuberculosis and HIV.