We present here the automated structure solution pipeline "autoSHARP." It is built around the heavy-atom refinement and phasing program SHARP, the density modification program SOLOMON, and the ARP/wARP package for automated model building and refinement (using REFMAC). It allows fully automated structure solution, from merged reflection data to an initial model, without any user intervention. We describe and discuss the preparation of the user input, the data flow through the pipeline, and the various results obtained throughout the procedure.

A single antibody was shown to adopt different binding-site conformations and thereby bind unrelated antigens. Analysis by both x-ray crystallography and pre-steady-state kinetics revealed an equilibrium between different preexisting isomers, one of which possessed a promiscuous, low-affinity binding site for aromatic ligands, including the immunizing hapten. A subsequent induced-fit isomerization led to high-affinity complexes with a deep and narrow binding site. A protein antigen identified by repertoire selection made use of an unrelated antibody isomer with a wide, shallow binding site. Conformational diversity, whereby one sequence adopts multiple structures and multiple functions, can increase the effective size of the antibody repertoire but may also lead to autoimmunity and allergy.

BUSTER±TNT is a maximum-likelihood macromolecular re®nement package. BUSTER assembles the structural model, scales observed and calculated structure-factor amplitudes and computes the model likelihood, whilst TNT handles the stereochemistry and NCS restraints/constraints and shifts the atomic coordinates, B factors and occupancies. In real space, in addition to the traditional atomic and bulk-solvent models, BUSTER models the parts of the structure for which an atomic model is not yet available (`missing structure') as lowresolution probability distributions for the random positions of the missing atoms. In reciprocal space, the BUSTER structure-factor distribution in the complex plane is a twodimensional Gaussian centred around the structure factor calculated from the atomic, bulk-solvent and missing-structure models. The errors associated with these three structural components are added to compute the overall spread of the Gaussian. When the atomic model is very incomplete, modelling of the missing structure and the consistency of the BUSTER statistical model help structure building and completion because (i) the accuracy of the overall scale factors is increased, (ii) the bias affecting atomic model re®nement is reduced by accounting for some of the scattering from the missing structure, (iii) the addition of a spatial de®nition to the source of incompleteness improves on traditional Luzzati and ' A -based error models and (iv) the program can perform selective density modi®cation in the regions of unbuilt structure alone.

Complement is an essential component of the innate and acquired immune system1, and consists of a series of proteolytic cascades that are initiated by the presence of micro-organisms. In health, activation of complement is precisely controlled through membrane-bound and soluble plasma-regulatory proteins including factor H (fH)2, a 155 kDa protein composed of twenty domains (termed complement control protein repeats, or CCPs). Many pathogens have evolved the ability to avoid immune- killing by recruiting host complement regulators3 and several pathogens have adapted to avoid complement-mediated killing by sequestering fH to their surface4. Here we present the first structure of a complement regulator in complex with its pathogen surface-protein ligand. This reveals how the important human pathogen Neisseria meningitidis subverts immune responses by mimicking the host, using protein instead of charged-carbohydrate chemistry to recruit the host complement regulator, factor H. The structure also indicates the molecular basis of the host-specificity of the interaction between factor H and the meningococcus, and informs attempts to develop novel therapeutics and vaccines.