With several major projects aimed at improving the choices and possibilities offered to external users of our end-stations completed and the foundations laid for structural biology at the ESRF post-EBS, 2017 has been another very busy year for the ESRF Structural Biology group. Indeed, all the group’s macromolecular crystallography (MX) facilities are now equipped with new generation FlexHCD sample changers, which, after initial teething troubles had been resolved, are faster, more reliable, versatile and robust than the SC3 devices they replace. Moreover, the completion of the ID23-2 nanobeam project means that the world’s first microfocus beamline dedicated to MX now provides users with a choice of two different beam sizes for experiments in micro-crystallography. However, the most high-profile project to be completed in our group in 2017 was the installation and commissioning of a Titan Krios cryo-electron microscope in the Belledonne Experimental Hall. As previously outlined, the microscope is being operated as a beamline (CM01) and forms part of the Partnership for Structural Biology (PSB) platform for cryo-electron microscopy (cryo-EM). Truly outstanding work by staff from the ESRF’s technical support divisions ensured that the infrastructure in which the microscope is sited was delivered on time and is second to none in terms of environmental stability (temperature, vibration, magnetic field), while excellent project management guaranteed the seamless installation and commissioning of the microscope. CM01 was inaugurated on 10th November 2017 with the first external user experiments starting soon after. Although it is still too soon to fully detail the outcomes of these, initial results, including those obtained on ‘test’ samples (i.e. Tobacco Mosaic Virus), are extremely encouraging and point to a very bright future for the beamline.

While all the above was being carried out, and as has been the case for many years, the ESRF’s facilities for structural biology continued to provide outstanding service to our external user community. ID29 and ID23-1 continue to be very productive with both end-stations delivering record numbers of depositions in the PDB (see http://biosync.sbkb.org/stats.do?stats_sec=RGNL&stats_focus_lvl=SITE&stats_site=ESRF for details). Output from the three UPBL10 MX end-stations (MASSIF-1 (ID30A-1), MASSIF-3 (ID30A-3) and ID30B) is also quickly ramping up, with the services they provide – particularly the ‘hands-off’, fully automatic data collection offered on MASSIF-1 – becoming very popular. 2017 has also seen BM29, the group’s BioSAXS beamline, truly come of age. When BM29 was first commissioned in 2012, BioSAXS was still seen as a ‘trendy’, but optional, technique complementary to MX. Such has been the success of BM29 – the number of papers citing use of the beamline is rapidly approaching 100 per year – that this is no longer the case and BioSAXS is now seen as a crucial source of complementary information in integrated structural biology projects, as are the in crystallo spectroscopy experiments provided by the group’s pioneering ID29S Cryobench facility, which was refurbished in 2017.

Experiments on structural biology end-stations account for ~40% of all experiments carried out at the ESRF with, as a natural consequence, external visitors (from academia and industry, remote or on-site) to these facilities making up a similar fraction of scientists carrying out experiments at the ESRF. However, we are well aware that scientific success is not purely a numbers game, and that it is quality of output that counts the most. We therefore hope that, as in previous years, the highlights reported here properly reflect the full range of the very high quality of research facilitated by experiments carried out on the Structural Biology group’s end-stations. As readers will see, an increasing proportion of this research is aimed at providing structural frameworks for the design of improved therapeutic agents, including new-generation antibiotics, in the treatment of disease. In addition to an increased focus on human health, the articles presented here detail investigations of fundamental biological processes including mechanisms used in signalling (see page 17) and in the regulation of gene expression (see page 20), the discovery and characterisation of an enzyme that converts fatty acids to hydrocarbons (see page 22) and perhaps most fundamental of all, at least in terms of new life, the structural basis of egg coat-sperm recognition at the moment of fertilisation (see page 29). One article – hopefully the first of many that will appear in future editions of the ESRF Highlights – reminds us that the study of structural biology at the ESRF is not limited to experiments exploiting MX, BioSAXS and cryo-EM (see page 26). Other techniques – in this case EXAFS experiments on BM01 – can be used to provide important structural information that helps further our understanding of the molecular mechanisms of disease.

By the time the 2018 edition of the ESRF Highlights appears, in January 2019, our users will have carried out the last experiments based on X-rays produced by the current ESRF storage ring. Future experiments will be carried out using ESRF-EBS (Extremely Brilliant Source), producing much brighter, more powerful X-ray beams than the current ESRF storage ring. The study of structural biology using this new source will be ensured both by the proper revision of many of our current beamlines, guaranteeing that they continue to provide state of the art end-stations (including world-leading automation and ancillary techniques) for structural biology, and by a major reconstruction, as agreed by the ESRF SAC in May 2018, of ID29. This reconstruction will provide, from late 2020, an ultra-high flux (~1016 photons/sec) micro/nanofocus facility for synchrotron serial crystallography (SSX) and time-resolved MX. Among many potential methods, the new beamline will facilitate the elucidation of SSX-derived room-temperature crystal structures that will deliver more information on the dynamics of biological macromolecules. These, combined with time-resolution on the microsecond timescale, will help provide ‘molecular’ movies of the conformational changes that are required in a multitude of biological processes.

G. Leonard and C. Mueller-Dieckmann