The impact of stable beamline automation can be seen in both the quality and quantity of this selection of highlights representing the work of the ESRF's structural biology community. Most of these excellent results would not have been possible without the tools put in place over the past decade. Limited space for this compilation has meant the omission of much work that is of extremely high standard. Nevertheless, several scientific themes do emerge. Whilst reaching the level of performance that we have been seeking – a task that has only been possible thanks to the combined efforts of all members of the Structural Biology Group, our colleagues at the EMBL in Grenoble and others elsewhere – 2010 marks the beginning of major changes in our beamline portfolio. Preparation of the new beamline complex on ID30 and BM29 is progressing fast, with the site prepared and construction underway. BM29 will become the new home for our Protein Solution Scattering beamline, benefiting from a wide wavelength range and a close interaction with both ID29 and ID30. We expect that the transfer from ID14-3 will be possible during 2011.  

The upgrade of the ESRF's structural biology facilities is based upon the premise that the resolution of challenging problems will require extensive access to synchrotron beamlines. Thus, the upgrade of our resources will provide new tools allowing both for the selection of the best crystals on which to carry out experiments and for the execution of the best possible experiment on the crystals selected. This approach will inevitably result in a change in the way in which projects are pursued. Many more samples will be examined before proper data collection and, once a plan for the best possible experiment has been developed, the relevant samples will be transferred to the most appropriate beamline for data collection. The first paper in this chapter covers initial work in this area and describes the detailed characterisation of protein crystals using “diffraction cartography”.

The study of macromolecular machines produces crystals that are extremely difficult to work with, however the reward for persistence is the exquisite beauty of the structures finally revealed and a number of  the contributions report on the fruits of very long term projects. Efremov et al. report the latest high resolution structure of the respiratory complex I from prokaryotes. This work combines information derived from crystal structures of the hydrophilic and membrane bound domains with that of the entire complex I to provide insights into the mechanism of action of this fundamental molecular machine. Illumination as to the basic chemistry and functional evolution of the ribosome is reported by Belousoff et al.. The conversion of solar energy into chemical bonds is essential for the survival of all higher life forms. Amunts et al. describe the latest results in their efforts to provide high resolution details of the plant photosystem I supercomplex. Extensive crystal screening and use of microbeams (with relatively large crystals) have enabled the group to extend the resolution of their structure to 3.3 Å. The crystal structure of the torque ring of the bacterial flagellar motor is reported by Lee et al. and provides a molecular basis for the explanation of rotational switching by this motor.

The structures of membrane-associated proteins also figure prominently among the highlights. The elucidation of the structure of the hydantoin transporter in its 'inward open' form completes the set for this transporter and has provided molecular details of the alternating access model of transport used by secondary active membrane transport proteins to harness electrochemical gradients to help effect the movement of small molecules or ions across membranes (Shimamura et al.). The localisation and movement of transmembrane proteins between different membranes in a cell is performed by the cell's vesicular transport system. The resolution of the structure of the AP2 clatherin adapter complex in an open, liganded form (Jackson et al.) follows on from the determination structure of the closed form of the complex (in 2002) and provides clear evidence for the complex's mechanism of action. Signal peptides play a role in directing proteins outside the cell. The crystal structure of a signal recognition particle 54 (SRP54) fused with a signal peptide (Yanda et al.) sheds light on the roles of Leu and Met side chains in the M domain of SRPs, in the binding of signal peptides with diverse sequences.

DNA binding is a feature of many proteins and is integral for the successful maintenance of cellular function. Three of the articles presented here examine various aspects of the roles of DNA binding proteins. These include the binding to mitochondrial DNA by the regulator mTERF (Jiménez-Menéndez et al.), a transcriptional regulation mechanism based on the ordering of intrinsically disordered domains upon DNA binding (Garcio-Pino et al.) and the repair of double stranded DNA breaks by the DNA dependent protein kinase (Sibanda et al.).

The discovery and development of new drugs is an important activity for both academic groups and pharmaceutical companies. Work toward the development of novel therapeutics for Leishmaniasis is reported (Frearson et al.), the structure characterisation of the nuclease domain of a herpesvirus terminase - a potential target for the development of antiviral molecules against herpesviruses - is described (Nadal et al.), and the mechanism of action of a new class of antibiotics is discussed (Bax et al.). The disruption of quorum sensing as a potential tool in the development of antimicrobial compounds is also addressed (Bokhove et al.). None of these results would have been possible without access to automated high intensity beamlines.

The study of spider silk has provided numerous examples of research using micro-beams, in particular on ID13. Askarieh et al. report the structure of a key protein responsible for forming the large assemblies involved in the formation of spider silk. Their model helps understand the pH regulation of the process. The diversity of life is demonstrated in the work of Hehemann et al., where analysis of high resolution crystal structures combined with bioinformatic detective work reveal an unexpected link between a marine porphyranase and a human gut bacterium present only in Japanese individuals!

Other reports in this chapter reveal the complementary nature of the ESRF's resources, the excellent service provided by the CRG beamlines and the international context within which the ESRF works. In many cases, the experimental data supporting the work is provided by more than one ESRF beamline or generated by combining data obtained at the ESRF and at other synchrotron centres. The future will see this trend increase. The demand for synchrotron beamtime for structural biology continues to increase and the productivity and imagination of this part of the ESRF's user community shows no signs of diminishing.

S. McSweeney and G. Leonard