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Related Experiment Videos

Phase changes in T(3)R(3)(f) human insulin: temperature or pressure induced?

G D Smith1, W A Pangborn, R H Blessing

  • 1Hauptman-Woodward Medical Research Institute, 73 High Street, Buffalo, NY 14203, USA. smith@hwi.buffalo.edu

Acta Crystallographica. Section D, Biological Crystallography
|July 27, 2001
PubMed
Summary

This study reveals the detailed low-temperature structure of human insulin hexamers, uncovering novel zinc ion coordination and conformational changes in key residues. These findings enhance our understanding of insulin

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Crystallography

Background:

  • Human insulin exists as hexamers crucial for storage and release.
  • Understanding insulin's structural dynamics is key to diabetes research.
  • Previous room-temperature structures provide a baseline for low-temperature analysis.

Purpose of the Study:

  • To determine the high-resolution structure of T(3)R(3) hexameric human insulin at 100 K.
  • To investigate conformational changes and zinc ion coordination at low temperatures.
  • To compare the low-temperature structure with its room-temperature counterpart.

Main Methods:

  • X-ray crystallography at 100 K using two different crystals.
  • High-resolution data collection (1.2 and 1.3 Å resolution).

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  • Refinement of the crystal structures.

    • Main Results:

    • Detailed structure of T(3)R(3) hexameric human insulin determined at 100 K.
    • Observed rotation of insulin dimers and displacements in R(f)-state monomers.
    • Identified four zinc ions on the threefold axis with varied coordination, including mixed tetrahedral/octahedral.
    • Discovered novel zinc binding sites at dimer interfaces and alternate HisB10 conformations.
    • Observed glycerol and water molecules in phenolic binding sites, alongside zinc ions and chloride in the second hexamer.
    • Evidence of protonation for a GluB13 side chain due to specific molecular contacts.

    Conclusions:

    • The low-temperature structure reveals distinct dimer orientations and monomer displacements compared to room temperature.
    • Novel zinc coordination environments and binding sites provide insights into insulin's stability and interactions.
    • The findings contribute to a deeper understanding of human insulin's structural behavior under different thermal conditions.