Table 4 Overview of structural investigation using XFEL facilities.
ProteinPurpose of the studyProtein classSize of crystalsResolution (Å)XFEL enablingReference
Photosystem IProof of conceptMembrane∼200–2 μm8.5NoChapman et al. [4]
LysozymeProof of conceptSoluble0.4 × 0.4 × 0.8 μm3<7.6NoLomb et al. [60]
Cathepsin B (TbCatB)Proof of conceptSoluble0.5–1 × 10–15 μm>8NoKoopmann et al. [77]
Photosystem I-FerredoxinTR-SFXMembrane500–2 µm?YesAquila et al. [78]
ThermolysinProof of conceptSoluble1 × 2 × 3 µm3>4NoSierra et al. [79]
LysozymeProof of conceptSoluble<1 × 1 × 3 μm31.9NoBoutet et al. [57]
Cathepsin B (TbCatB)Structure elucidationSoluble1 × 1 × 11 μm32.1YesRedecke et al. [80]
LysozymeProof of conceptSolubleMicrocrystals3.2NoBarends et al. [38]
30S ribosomal subunitProof of conceptSoluble3 × 5 × 200 μm3>6NoDemirci et al. [81]
Photosynthetic reaction centre from Blastochloris viridis (RCvir)Comparison with room temperature structureMembraneMicrocrystals3.5NoJohansson et al. [58]
Serotonin receptor 5-HT2BProof of conceptMembrane5 × 5 × 5 μm32.8NoLiu et al. [43]
LysozymeProof of conceptSoluble<1 × 1 × 2 μm32.1NoBarends et al. [82]
Smoothened receptorProof of conceptMembrane<5 μm3.2YesWeierstall et al. [73]
Cytochrome c oxidaseRadiation damage freeMembraneNot reported1.9YesHirata et al. [83]
Photosystem II ThermolysinTR-SFXMembrane5 × 5–10 μm4.5YesKern et al. [84]
SolubleNot reported1.8No
Cry3A toxin from Bacillus thuringiensis (Bt)Proof of conceptSoluble1.5 × 1.0 × 0.5 μm32.8NoSawaya et al. [76]
Photosystem II from Tricondyloides elongatusTR-SFXMembrane1 μm5YesKupitz et al. [85]
LysozymeEvaluation of grease matrix as carrier mediumSoluble7–10 μm2NoSugahara et al. [86]
Glucose isomeraseSoluble10–30 μm2No
ThaumatinSoluble10–30 μm2No
FABP3Soluble10–20 μm2No
Cpl hydrogenaseProof of concept, goniometer-basedSoluble>400 μm1.6NoCohen et al. [23]
MyoglobinSoluble?1.4No
β2-Adrenoreceptor/ Complex with nanobodyMembrane20–100 µm2.8No
RNA polymerase II complexSoluble0.5–3 μm3.3No
Photoactive yellow proteinTR-SFXSoluble1–5 μm1.6YesKupitz et al. [48]
Clostridium ferredoxinIndication of radiation damage in XFELSoluble1–1.6 × 1–1.6 × 5–17 μm32NoNass et al. [61]
δ-opioid receptorHigher resolution achieved compared with synchrotron structureMembrane∼5 µm2.7NoFenalti et al. [34]
Angiotensin IIStructure-based drug designMembrane4 × 4 × 40 μm32.9YesZhang et al. [71]
CPV17 polyhedrinStructure determinationSolubleYesGinn et al. [87]
Ca2+-ATPase SERCAProof of conceptMembrane2 × 2 × 10–50 µm2.8NoBublitz et al. [70]
Phycocyanin from T. elongatusNovel inert crystal delivery mediumSoluble1–5 µm2.5NoCoquelle et al. [24]
LysozymeProof of concept, LCP as carrier mediumSoluble1 × 1 × 2 μm31.9NoFromme et al. [88]
PhycocyaninSoluble10 × 10 × 5 μm31.75
Rhodospin/arrestin complexStructure determinationMembrane5–10 μm3.8 along a and b axis and 3.3 along the cYesKang et al. [72]
Luciferin-regenerating enzymeProof of concept, de novo phasingSoluble2–5 × 10–30 µm1.5NoYamashita et al. [89]
Cyclophilin A (CypA)Room temperatureSoluble1.75YesKeedy et al. [90]
Cytochrome c peroxidase (CCP) compound I (CmpI)Radiation-damage free structureSoluble150 µ–1mm1.5YesChreifi et al. [91]
LysozymeProof of concept, liquid-droplet injectorSoluble5 µm2.3NoMiyajima et al. [92]
LysozymeProof of concept, Acoustic levitatorSoluble5–100 µm2.13NoRoessler et al. [93]
Thermolysin10–100 µm2.52
Stachydrine demethylase25–300 µm2.2
A2A receptorProof of concept, S-SAD phaseMembrane5 × 5 × 2 μm31.9NoBatyuk et al. [40]
BacteriorhodopsinTR-SFXMembraneNot reported2.0YesNango et al. [46]
Granulovirus occlusion bodiesProof of conceptSoluble<0.016 μm32NoGati et al. [94]
Photosystem IITR-SFXMembrane<100 µm in length2.35YesSuga et al. [95]
Proteinase KProof of conceptSoluble8–12 µm1.2NoMasuda et al. [37]
LysozymeProof of concept, hydroxycellulose matrixSoluble1 × 1 × 1 μm31.45NoSugahara et al. [26]
Thaumatin2 × 2 × 4 μm31.55
Proteinase K4 × 4 × 4–5 × 5 × 7 μm31.5
ThermolysinProof of concept, soakingSoluble4 × 4 × 8 μm32NoNaitow et al. [44]
Picornavirus bovine enterovirus 2 polyhedrosis virus type 18 polyhedrinProof of concept, fixed targetSoluble8 × 8 × 8 μm3<4 μM2.3 2.4NoRoedig et al. [96]
Cytochrome c oxidaseTR-SFXSoluble100 × 500 μm2.2YesShimada et al. [97]
A2A receptorSerial crystallography at XFEL compared with synchrotronMembrane30 × 30 × 5 μm31.7NoWeinert et al. [35]

  • Initially, some reference proteins were investigated using an XFEL to establish sample delivery and X-ray diffraction analysis. Targets highlighted in bold are GPCR structural studies relevant to drug discovery which have been reported so far.