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Updated: Jul 2, 2025

Selection of Aptamers for Amyloid β-Protein, the Causative Agent of Alzheimer's Disease
15:23

Selection of Aptamers for Amyloid β-Protein, the Causative Agent of Alzheimer's Disease

Published on: May 13, 2010

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Binding site prediction between lysozyme and glucose-regulated protein 78, a hope to fight amyloidosis

Ahmed M Elgharib1, Wael M Elshemey2, Abdo A Elfiky1

  • 1Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt.

Journal of Biomolecular Structure & Dynamics
|February 23, 2024
PubMed

Insights

This study identifies a binding site between human lysozyme and GRP78, a key protein in the quality control system. This discovery offers a potential strategy for developing drugs to prevent amyloidosis by clearing misfolded lysozyme proteins.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Computational Biology

Background:

  • Amyloidosis involves organ failure from misfolded protein precipitation.
  • The protein quality control (PQC) system, including GRP78, helps clear damaged proteins.
  • Mutated lysozyme variants are implicated in forming amyloid fibrils.

Purpose of the Study:

  • To computationally investigate binding sites between human lysozyme and GRP78.
  • To understand how lysozyme mutations affect protein aggregation and amyloid formation.

Main Methods:

  • Structural bioinformatics analysis.
  • Molecular dynamics simulations.
  • Multiple sequence alignment (MSA).

Main Results:

  • A favorable binding interaction was identified between the lysozyme cyclic region (C65-C81) and GRP78's substrate binding domain (SBD).
  • Lysozyme mutations showed varied interactions and binding patterns with GRP78, correlating with aggregation propensity.
  • The C65-C81 region of lysozyme shares similarity with cyclic Pep42.

Conclusions:

  • A specific lysozyme-GRP78 binding site is proposed.
  • This finding could guide drug design for targeted removal of misfolded lysozyme, preventing amyloidogenesis.
Keywords:
AmyloidosisGRP78lysozymemolecular dynamic simulationprotein–protein dockingstructural bioinformatics

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