Related Experiment Video
Updated: May 22, 2026

Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
Nucleobindin 1 caps human islet amyloid polypeptide protofibrils to prevent amyloid fibril formation
Ruchi Gupta1, Neeraj Kapoor, Daniel P Raleigh
1Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
Abstract:
Many human diseases are associated with amyloid fibril deposition, including type 2 diabetes mellitus where human islet amyloid polypeptide (hIAPP) forms fibrils in the pancreas. We report here that engineered, soluble forms of the human Ca(2+)-binding protein nucleobindin 1 (NUCB1) prevent hIAPP fibril formation and disaggregate preexisting hIAPP fibrils. Scanning transmission electron microscopy (STEM) and atomic force microscopy indicate that NUCB1 binds to and stabilizes heterogeneous prefibrillar hIAPP species. The NUCB1-stabilized prefibrillar species were isolated by size-exclusion chromatography and analyzed by STEM, dynamic light scattering, and multi-angle light scattering. The stabilized prefibrillar species show a size range of 2-6 million Da and have other similarities to hIAPP protofibrils, but they do not progress to become mature fibrils. The effects of NUCB1 are absent in the presence of Ca(2+). We postulate that the engineered forms of NUCB1 prevent hIAPP fibril formation by a mechanism where protofibril-like species are "capped" to prevent further fibril assembly and maturation. This mode of action appears to be different from other protein-based inhibitors, suggesting that NUCB1 may offer a new approach to inhibiting amyloid formation and disaggregating amyloid fibrils.
Related Concept Videos
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Insulin: Biosynthesis, Chemistry, and Preparation
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
Protein and Protein Structure
A protein's shape is critical to its function. For example, an enzyme can...
Insulin Secretory Vesicles
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
Insulin and C-peptide are co-secreted in...

