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Sleeping sickness is a fatal disease caused by the protozoan parasite Trypanosoma brucei (Tb). Inosine-5'-monophosphate dehydrogenase (IMPDH) has been proposed as a potential drug target, since it maintains the balance between guanylate deoxynucleotide and ribonucleotide levels that is pivotal for the parasite. Here we report the structure of TbIMPDH at room temperature utilizing free-electron laser radiation on crystals grown in living insect cells. The 2.80 Å resolution structure reveals the presence of ATP and GMP at the canonical sites of the Bateman domains, the latter in a so far unknown coordination mode. Consistent with previously reported IMPDH complexes harboring guanosine nucleotides at the second canonical site, TbIMPDH forms a compact oligomer structure, supporting a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity. The oligomeric TbIMPDH structure we present here reveals the potential of in cellulo crystallization to identify genuine allosteric co-factors from a natural reservoir of specific compounds.

Supplement: 1, Meeting Abstract: P-177

Contains fulltext : 154870.pdf (publisher's version ) (Closed access), Rhodopsin is the G protein-coupled receptor (GPCR) that serves as a dim-light receptor for vision in vertebrates. We probed light-induced conformational changes in rhodopsin in its native membrane environment at room temperature using time-resolved wide-angle x-ray scattering. We observed a rapid conformational transition that is consistent with an outward tilt of the cytoplasmic portion of transmembrane helix 6 concomitant with an inward movement of the cytoplasmic portion of transmembrane helix 5. These movements were considerably larger than those reported from the basis of crystal structures of activated rhodopsin, implying that light activation of rhodopsin involves a more extended conformational change than was previously suggested.

Contains fulltext : 154870.pdf (publisher's version ) (Closed access), Rhodopsin is the G protein-coupled receptor (GPCR) that serves as a dim-light receptor for vision in vertebrates. We probed light-induced conformational changes in rhodopsin in its native membrane environment at room temperature using time-resolved wide-angle x-ray scattering. We observed a rapid conformational transition that is consistent with an outward tilt of the cytoplasmic portion of transmembrane helix 6 concomitant with an inward movement of the cytoplasmic portion of transmembrane helix 5. These movements were considerably larger than those reported from the basis of crystal structures of activated rhodopsin, implying that light activation of rhodopsin involves a more extended conformational change than was previously suggested.

Contains fulltext : 154870.pdf (publisher's version ) (Closed access), Rhodopsin is the G protein-coupled receptor (GPCR) that serves as a dim-light receptor for vision in vertebrates. We probed light-induced conformational changes in rhodopsin in its native membrane environment at room temperature using time-resolved wide-angle x-ray scattering. We observed a rapid conformational transition that is consistent with an outward tilt of the cytoplasmic portion of transmembrane helix 6 concomitant with an inward movement of the cytoplasmic portion of transmembrane helix 5. These movements were considerably larger than those reported from the basis of crystal structures of activated rhodopsin, implying that light activation of rhodopsin involves a more extended conformational change than was previously suggested.

Serial femtosecond crystallography is an X-ray free-electron-laser-based method with considerable potential to have an impact on challenging problems in structural biology. Here we present X-ray diffraction data recorded from microcrystals of the Blastochloris viridis photosynthetic reaction centre to 2.8 Å resolution and determine its serial femtosecond crystallography structure to 3.5 Å resolution. Although every microcrystal is exposed to a dose of 33 MGy, no signs of X-ray-induced radiation damage are visible in this integral membrane protein structure.

Contains fulltext : 76147.pdf (publisher's version ) (Closed access)

Contains fulltext : 76147.pdf (publisher's version ) (Closed access)

Exciton dynamics in chiral helixes of an oligo-p-phenylenevinylene deriv. monofunctionalized with a ureido-s-triazine (MOPV) were studied. The latter functional group leads to oligomer dimerization by hydrogen bonding in dodecane soln., resulting in reversible supramol. assembly by solvophobic and p-p interactions. MOPV is a model system to study exciton transfer dynamics as it is possible to study the effect of intermol. interactions by comparing optical properties in the dissolved phase (above the transition temp.) and the supramol. assemblies. The model allows to ext. microscopic informations such as the av. exciton hopping annihilation rates. It is believed that this model also allows the quant. description of the exciton dynamics on supramol. architectures from subpicosecond to nanosecond timescales.

Exciton dynamics in chiral helixes of an oligo-p-phenylenevinylene deriv. monofunctionalized with a ureido-s-triazine (MOPV) were studied. The latter functional group leads to oligomer dimerization by hydrogen bonding in dodecane soln., resulting in reversible supramol. assembly by solvophobic and p-p interactions. MOPV is a model system to study exciton transfer dynamics as it is possible to study the effect of intermol. interactions by comparing optical properties in the dissolved phase (above the transition temp.) and the supramol. assemblies. The model allows to ext. microscopic informations such as the av. exciton hopping annihilation rates. It is believed that this model also allows the quant. description of the exciton dynamics on supramol. architectures from subpicosecond to nanosecond timescales.