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Updated: Jun 19, 2026
07:09
Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States
Published on: April 1, 2015
Molecular basis for insulin fibril assembly.
Magdalena I Ivanova1, Stuart A Sievers, Michael R Sawaya
1Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Los Angeles CA 90095-1570, USA.
Summary
A specific insulin segment, LVEALYL, drives amyloid fibril formation in injection amyloidosis. Understanding this segment
Area of Science:
- Biochemistry
- Structural Biology
- Medical Conditions
Background:
- Injection amyloidosis is a rare condition characterized by extracellular insulin fibrils.
- The molecular mechanisms underlying insulin fibrillation are not fully understood.
Purpose of the Study:
- To identify the minimal segment of insulin responsible for fibril nucleation and inhibition.
- To elucidate the structural basis of insulin fibril formation at high resolution.
Main Methods:
- Investigated the fibrillation properties of a specific insulin B-chain segment (LVEALYL).
- Determined the atomic resolution (1 Å) structure of isolated LVEALYL aggregates.
- Utilized electron microscopy, X-ray fiber diffraction, and biochemical assays.
Main Results:
- The LVEALYL segment was identified as the smallest unit that both nucleates and inhibits insulin fibrillation in a molar ratio-dependent manner.
- Isolated LVEALYL forms microcrystalline aggregates with fibrillar morphology.
- The determined structure reveals stacked LVEALYL segments forming pairs of interdigitated beta-sheets with a dry steric zipper interface.
Conclusions:
- The LVEALYL segment is central to the cross-beta spine of insulin fibrils.
- The high-resolution structure of LVEALYL aggregates provides a detailed model for human insulin fibrils.
- This finding offers insights into the pathogenesis of injection amyloidosis and potential therapeutic targets.
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