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TOP 5 BIOLOGICAL MOLECULAR STRUCTURES EVER SOLVED

Structure reveals function—driving breakthroughs in biology, chemistry, and medicine.

PUSHING THE LIMITS OF MOLECULAR RESOLUTION

Understanding molecular structure is key to understanding function. By revealing the precise arrangement of atoms, structural biology enables scientists to uncover how proteins and small molecules work, how diseases develop, and how new therapies can be designed. Continued advances in imaging and detection technologies are pushing the limits of resolution, allowing researchers to visualize biological machinery in unprecedented detail. As a manufacturer of high-performance direct detection cameras supporting these discoveries, we’re inspired by the breakthroughs made possible through structural imaging. Here, we highlight five landmark molecular structures whose extraordinary resolution has expanded the boundaries of science.

Resolution Structure Technique Detector Authors Radiation Source
0.48 Å
Small protein crambin
X-Ray Diffraction
MAR CCD 165 mm
Schmidt, A.,
Teeter, M., Weckert, E.,
Lamzin, V.S.
PETRA II, DESY BEAMLINE PETRA1

Figure 1: Small (4.92 kDa – 46 amino acids), rigid, highly ordered structure that diffracts to extremely high resolution makes it a good benchmark molecule. Biologically, crambin is a small seed protein from Crambe abyssinica that functions as a seed-storage and protective protein.

Resolution Structure Technique Detector Authors Radiation Source
0.48 Å
High-potential iron-sulfur protein
X-Ray Diffraction
RAYONIX CCD MX225HE
Hirano, Y., Takeda, K.,
Miki, K., Lamzin, V.S.
SPRING-8 BEAMLINE BL41XU

Figure 2: Ultra-high resolution (0.48 Å) X-ray structure of a high-potential iron–sulfur protein (HiPIP) with the distribution of valence electrons in addition to atom positions. Such features go beyond typical high resolution structures and reveal detailed electronic and bonding features in a biological electron-transfer center.

Resolution Structure Technique Detector Authors Radiation Source
0.5 Å
Sodium glutamate
Micro-ED
Direct Electron Apollo
Takuma Fukumura;
Takanori Nakane; Yuji Konyuba;
Benjamin Bammes
JEOL CryoARM 300 II

Figure 3: Positions of all atoms including hydrogens are visible in the ultra-high resolution (0.5 Å) electron density map. Significant as data was collected with an advanced MAPS detector (Apollo) using a conventional but powerful TEM (CryoARM300-2) rather than a synchrotron. Biologically, MSG is an important food additive/flavor enhancer and better understanding the structure can provide insight into taste receptors and other metabolic/neurological areas of research.

Resolution Structure Technique Detector Authors Radiation Source
0.5 Å
Histidine
Micro-ED
Direct Electron Apollo
Takuma Fukumura;
Takanori Nakane; Yuji Konyuba;
Benjamin Bammes
JEOL CryoARM 300 II

Figure 4: Strong low-frequency reflections require high counting rates to avoid coincidence loss but also high sensitivity to detect the very weak high-resolution reflections – Apollo handles both simultaneously. Improved resolution in histidine structures enables direct observation/placement of hydrogen atoms, unambiguous assignment of protonation and tautomeric states, and accurate electrostatic and bonding analysis.

Resolution Structure Technique Detector Authors Radiation Source
0.54 Å
Small protein crambin
X-Ray Diffraction
Image Plate Mar Research
Jelsch, C., Teeter, M.M.,
Lamzin, V., Pichon-Lesme,
V., Blessing, B., Lecomte, C.
EMBL/DESY,
Hamburg Beamline BW7A

Figure 5: Biologically, crambin is a small seed protein from Crambe abyssinica that functions as a seed-storage and protective protein.

Techniques

  • Cryo-EM single particle analysis: flash-frozen biomolecules are imaged in vitreous ice in a TEM. Thousands to millions of images are computationally combined to reconstruct 3D structures without the need for crystals.
  • X-ray diffraction: diffraction patterns are obtained from highly ordered crystals of a molecule placed in a synchrotron beamline, and are used to determine its atomic structure.
  • Micro-ED: applies electron diffraction to extremely small 3D crystals under cryogenic conditions, enabling structure determination of proteins, peptides, and small molecules that are too tiny for traditional X-ray diffraction.

 

References:

  1. Schmidt, A., Teeter, M., Weckert, E., & Lamzin, V. (2011). Crystal structure of small protein crambin at 0.48Å resolution. Acta Crystallographica Section F, 67(4), 424–428.
  2. Hirano, Y., Takeda, K. & Miki, K. Charge-density analysis of an iron–sulfur protein at an ultra-high resolution of 0.48 Å. Nature 534, 281–284 (2016). https://doi.org/10.1038/nature18001
  3. https://doi.org/10.51093/xrd-00140, https://x.com/biochem_fan/status/1605896384304975872
  4. https://doi.org/10.51093/xrd-00141, To Do: https://directelectron.com/apollo-sets-record-for-microed-resolution/
  5. C. Jelsch, M.M. Teeter, V. Lamzin, V. Pichon-Pesme, R.H. Blessing, & C. Lecomte, Accurate protein crystallography at ultra-high resolution: Valence electron distribution in crambin, Proc. Natl. Acad. Sci. U.S.A. 97 (7) 3171-3176, https://doi.org/10.1073/pnas.97.7.3171 (2000).
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