Related Experiment Video

Updated: Aug 15, 2026

Rapid Generation of Amyloid from Native Proteins In vitro
05:48

Rapid Generation of Amyloid from Native Proteins In vitro

Published on: December 5, 2013

Interaction of amyloid beta-protein with anionic phospholipids: possible involvement of Lys28 and C-terminus

A Chauhan1, I Ray, V P Chauhan

  • 1New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314-6399, USA.

Neurochemical Research
|April 13, 2000
PubMed

Insights

Acidic phospholipids, particularly those with phosphate groups, accelerate amyloid beta-protein (Abeta) fibrillization, a key process in Alzheimer's disease (AD). This interaction involves specific Abeta regions and lipid components.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Molecular Biology

Background:

  • Amyloid plaques composed of fibrillar amyloid beta-protein (Abeta) are hallmarks of Alzheimer's disease (AD).
  • The precise mechanism driving the fibrillization of soluble Abeta in AD remains unclear.
  • Lipid interactions are increasingly recognized as potential modulators of Abeta aggregation.

Purpose of the Study:

  • To investigate the influence of various lipid types on the fibrillization of Abeta 1-40.
  • To identify specific lipid features and Abeta structural elements critical for Abeta-lipid interactions.

Main Methods:

  • Studied the effect of neutral, zwitterionic, and anionic lipids on Abeta 1-40 fibrillization.
  • Utilized fluorescence assays with NBD-labeled phospholipids (NBD-PA and NBD-PE) to probe Abeta-lipid binding.
  • Examined the interaction of various Abeta peptides with NBD-PA to map critical regions.

Main Results:

  • Acidic phospholipids containing phosphate groups (e.g., phosphatidylserine, cardiolipin) significantly increased Abeta fibrillization.
  • Neutral lipids, zwitterionic lipids, and anionic lipids lacking phosphate groups did not affect Abeta fibrillization.
  • Abeta peptides demonstrated specific binding to NBD-PA, with longer forms (Abeta 1-43, Abeta 1-42) showing stronger interaction than shorter forms.
  • The C-terminus of Abeta, including phosphate-binding sites and fatty acid-interacting aliphatic amino acids, is crucial for interaction with anionic phospholipids.

Conclusions:

  • Phosphate groups and specific structural features of Abeta are essential for its interaction with anionic phospholipids, promoting fibrillization.
  • Lysine 28 and the C-terminal aliphatic residues of Abeta play key roles in anchoring to and interacting with phospholipids.
  • Understanding these lipid-mediated mechanisms could offer new therapeutic targets for Alzheimer's disease.

More Related Videos

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis06:17

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis

Published on: May 22, 2018

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils15:04

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Published on: September 28, 2019

Related Concept Videos

Amino acids03:42

Amino acids

Amino acids are the monomers that comprise proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom, or the alpha (α) carbon, bonded to an amino group (NH2), a carboxyl group (COOH), and to a hydrogen atom. Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group. There are 20 common amino acids present in proteins, each with a different R group. Variation in the amino acid sequence is responsible for...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called 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...
Oligosaccharide Assembly01:24

Oligosaccharide Assembly

Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called 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...