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 Concept Videos

Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

113.9K
Overview
113.9K
Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

12.8K
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
12.8K
The Early Endosome: Endocytosis of Transferrin01:28

The Early Endosome: Endocytosis of Transferrin

5.3K
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
5.3K
Signal Sequences and Sorting Receptors01:41

Signal Sequences and Sorting Receptors

15.9K
Signal sequences are short amino acid sequences that guide newly synthesized proteins to their proper location within the cell. Classical signal sequences are fifteen to sixty amino acids long and present at the N-terminus of a polypeptide chain. Each signal sequence has a conserved segment of basic residues towards their N terminus, a hydrophobic core, and a C-terminus rich in polar residues. The C-terminus also contains a signal cleavage site and features a -3 -1 sequence motif. The -3-1...
15.9K
Amyloid Fibrils03:03

Amyloid Fibrils

13.2K
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,...
13.2K
Amyloid Fibrils03:03

Amyloid Fibrils

7.0K
7.0K

You might also read

Related Articles

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

Sort by
Same author

Emergence of functional prey depletion halo through penguin-krill behavioural dynamics.

Proceedings. Biological sciences·2026
Same author

A Novel Near-Infrared Fluorescence Vaginal Pipe (LunaPipe) for Navigation in Robot-Assisted Total Hysterectomy.

Journal of minimally invasive gynecology·2026
Same author

Direct Selection of Functional De Novo Macrocycles for Activation of On-Cellulo Insulin Receptor.

Angewandte Chemie (International ed. in English)·2026
Same author

Functional and Structural Characterization of a Novel Anti-His-tag Antibody, HisMab-1.

Journal of molecular biology·2025
Same author

Muscle-specific tyrosine kinase activation by a peptide-based dimerizer is orientation dependent.

Structure (London, England : 1993)·2025
Same author

Ovarian metastases from renal cell carcinoma: A report of two cases.

Fujita medical journal·2025

Related Experiment Video

Updated: Apr 18, 2026

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

7.7K

Structural basis for amyloidogenic peptide recognition by sorLA.

Yu Kitago1, Masamichi Nagae1, Zenzaburo Nakata1

  • 1Institute for Protein Research, Osaka University, Suita, Japan.

Nature Structural & Molecular Biology
|February 3, 2015
PubMed
Summary

SorLA, a risk factor for Alzheimer's disease, binds amyloid-beta (Aβ) peptides. Structural analysis reveals SorLA's Vps10p domain captures Aβ via a tunnel, suggesting broad specificity for beta-sheet forming peptides.

More Related Videos

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
07:55

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP

Published on: October 17, 2015

12.5K
Detection of Detergent-sensitive Interactions Between Membrane Proteins
10:09

Detection of Detergent-sensitive Interactions Between Membrane Proteins

Published on: March 7, 2018

6.5K

Related Experiment Videos

Last Updated: Apr 18, 2026

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

7.7K
Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
07:55

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP

Published on: October 17, 2015

12.5K
Detection of Detergent-sensitive Interactions Between Membrane Proteins
10:09

Detection of Detergent-sensitive Interactions Between Membrane Proteins

Published on: March 7, 2018

6.5K

Area of Science:

  • Neuroscience
  • Structural Biology
  • Molecular Biology

Background:

  • SorLA (Sortilin-related receptor 1) is a neuronal sorting receptor implicated as a risk factor in Alzheimer's disease (AD).
  • Previous research established SorLA's role in the lysosomal targeting of neurotoxic amyloid-beta (Aβ) peptides through direct binding.
  • Understanding the molecular mechanism of Aβ binding by SorLA is crucial for developing therapeutic strategies against AD.

Purpose of the Study:

  • To determine the crystal structure of the human sorLA Vps10p domain, responsible for Aβ capture.
  • To elucidate the structural basis of Aβ binding by SorLA.
  • To investigate the binding specificity of SorLA Vps10p towards Aβ peptides.

Main Methods:

  • X-ray crystallography was employed to determine the structure of the human sorLA Vps10p domain.
  • Structures were solved for the Vps10p domain in an unbound state and in complex with two different ligands.
  • The structure of the sorLA Vps10p-Aβ complex was analyzed to understand ligand binding interactions.

Main Results:

  • The human sorLA Vps10p domain adopts a ten-bladed β-propeller fold with a central tunnel.
  • An internal ligand, derived from the sorLA propeptide, binds within the tunnel, extending a β-sheet.
  • The crystal structure of the sorLA Vps10p-Aβ complex shows that Aβ peptides bind to the same site within the tunnel.
  • SorLA Vps10p recognizes peptides through redundant binding modes, indicating broad specificity for peptides prone to β-sheet formation.

Conclusions:

  • The Vps10p domain of SorLA utilizes a conserved binding site within its central tunnel for capturing amyloid-beta peptides.
  • SorLA exhibits broad specificity for Aβ peptides, recognizing them via interactions that do not strictly depend on specific amino acid sequences.
  • These findings provide critical structural insights into SorLA's role in Alzheimer's disease pathogenesis and suggest potential therapeutic targets.