Instruct provides open access to technologies at institutional, regional or national facilities representing the most advance or specialist in the field of structural biology. Access is through the online proposal submission portal. The overarching criterion for approval is scientific excellence. Instruct funded access to the infrastructure requires agreement to publish data, duly acknowledged, arriving from the work undertaken at a Centre. Outcomes from the programme to date demonstrate success with hundreds of peer-reviewed publications.
Title: Nanobodies against Vps34 complexes
Publication arising from Instruct proposal: PID 1279
We received complexes containing Vps15/Vps30/Vps34/Atg14 and Vps15/Vps30/Vps34/Vps38. These two complexes known as complexes I and II, respectively control initiation of autophagy and endocytic traffic in cells. Both complexes are about 400 kDa. The Williams lab want to determine their structures so that they can develop inhibitors and activators that could have applications in cancer therapy and neurodegeneration. They carried out extensive crystallisation trials for these complexes, both by themselves and in complexes with inhibitors without success. The Williams lab want to try co-crystallisation with nanobodies, as this has been very successful for their previous work. We immunized 2 separate llamas and generated nanobodies against both complexes. For complex II, we selected nanobodies on cross linked and non-cross linked material. Finally, the platform provided about 30 nanobody plasmids. The Williams lab could express all nanobodies. The HDX-MS worked well and provided useful information on epitope-binding sites. Crystals for complex II were obtained and a structure was refined
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Instruct activities are delivered by the Instruct Centres distributed across the national Members, mostly embedded in high education institutions. The centres provide the organisational framework to deliver Instruct activities to researchers and other stakeholders.
FRISBI, Instruct Centre France
FRISBI is a National Infrastructure in Biology and Health that coordinates a national network of integrated structural biology. Integrated structural biology combines structural data from different physical techniques, both cellular and in vitro, to understand how protein complexes or pathogens (e.g. viruses and bacteria) interact with their environment within the cell.
Article in Nature by Ewen Callaway: Structural biologists share their toys. The article describe Instruct path to operations.