Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

A native to amyloidogenic transition regulated by a backbone trigger.

Catherine M Eakin1, Andrea J Berman, Andrew D Miranker

  • 1Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, Connecticut 06520-8114, USA.

Nature Structural & Molecular Biology
|February 24, 2006
PubMed
Summary

Researchers identified how beta-2-microglobulin (beta2m) forms amyloid fibers, revealing a key proline isomerization catalyzed by metal ions. This discovery enables the study of fibrillogenesis intermediates.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

African Green Monkeys Respond to Synthetic Aβ Oligomers with Persistent Alzheimer's-like Activation.

bioRxiv : the preprint server for biology·2025
Same author

Identification of missense DMC1 variants in males with non-obstructive azoospermia.

Journal of assisted reproduction and genetics·2025
Same author

Comparative analysis of the LARP1 C-terminal DM15 region through Coelomate evolution.

PloS one·2024
Same author

Effects of <i>Tcte1</i> knockout on energy chain transportation and spermatogenesis: implications for male infertility.

Human reproduction open·2024
Same author

Heterozygous TP63 pathogenic variants in isolated primary ovarian insufficiency.

Journal of assisted reproduction and genetics·2023
Same author

Genomic study of <i>TEX15</i> variants: prevalence and allelic heterogeneity in men with spermatogenic failure.

Frontiers in genetics·2023

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Background:

  • Amyloid fibers are linear protein aggregates implicated in various diseases.
  • Understanding fibrillogenesis, the process of fiber formation, is crucial but challenging due to transient intermediates.

Purpose of the Study:

  • To elucidate the conformational changes initiating beta-2-microglobulin (beta2m) fibril formation in dialysis-related amyloidosis.
  • To determine the atomic-level mechanism of amyloid assembly initiation.

Main Methods:

  • Investigated beta-2-microglobulin (beta2m) in dialysis-related amyloidosis.
  • Utilized divalent cation binding to study amyloidogenic conformations.
  • Designed and characterized a beta2m variant mimicking the fibrillogenic intermediate.

Related Experiment Videos

Main Results:

  • Divalent cation binding catalyzes beta2m access to amyloidogenic conformations.
  • Backbone isomerization of a conserved proline residue is the chemical basis for this process.
  • A stable, folded beta2m variant mimicking the intermediate state was created and analyzed.

Conclusions:

  • The study reveals the precise initiating conformational changes for beta2m amyloid assembly at atomic resolution.
  • The designed beta2m variant serves as a stable model for studying fibrillogenesis intermediates.
  • Findings provide critical insights into the mechanism of amyloid fiber formation.