Related Experiment Video
Updated: Jul 20, 2026
06:45
Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
Published on: May 26, 2011
Calcitonin forms oligomeric pore-like structures in lipid membranes
Marco Diociaiuti1, Laura Zanetti Polzi, Luisa Valvo
1Dipartimento di Tecnologie e Salute, Istituto Superiore di Sanità, 299-00161 Rome, Italy. marco.diociaiuti@iss.it
Biophysical Journal
|August 31, 2006
Summary
Salmon-calcitonin (sCT) forms amyloid-like oligomers that create ion channels in cell membranes. These channels facilitate calcium (Ca2+) entry, potentially impacting bone metabolism.
Area of Science:
- Biochemistry
- Structural Biology
- Membrane Biophysics
Background:
- Calcitonin (CT) is a hormone regulating calcium metabolism.
- Amyloid proteins, including those in neurodegenerative diseases, share a propensity to aggregate into beta-sheet structures.
- The aggregation and membrane interactions of CT are not fully understood.
Purpose of the Study:
- To investigate the aggregation of salmon-calcitonin (sCT) into oligomeric structures.
- To examine the interaction of sCT with model membranes, particularly lipid rafts.
- To determine the functional consequences of sCT aggregation, specifically its ion channel activity.
Main Methods:
- Transmission electron microscopy (TEM) to visualize sCT oligomers and their membrane interactions.
- TEM immunogold labeling for protein localization.
- Circular dichroism (CD) spectroscopy to analyze protein secondary structure.
- Spectrofluorimetry using Fluo-4 to measure calcium (Ca2+) ion flux.
Main Results:
- sCT forms annular oligomers structurally similar to amyloid-beta and alpha-synuclein.
- Lipid rafts (cholesterol and GM1) enhance sCT binding to membranes.
- sCT oligomers form pore-like structures in membranes and increase beta-sheet content.
- sCT oligomers facilitate Ca2+ entry into raft-mimicking liposomes, indicating ion channel activity.
Conclusions:
- Salmon-calcitonin oligomers exhibit amyloid-like aggregation and form functional ion channels.
- These sCT-induced ion channels allow Ca2+ permeation across membranes.
- The formation of Ca2+ channels by sCT oligomers may represent an additional mechanism for calcium regulation in bone cells.
More Related Videos
Related Concept Videos
00:51Synthesis and Functions of Calcitonin
Calcitonin, a vital polypeptide hormone, regulates calcium levels within body fluids. It is released by the parafollicular cells, also known as C cells, situated in the follicular epithelium of the thyroid gland. Calcitonin responds to fluctuations in blood calcium levels and the influence of gastrointestinal hormones like gastrin and cholecystokinin.
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
01:21Structure of Porins
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel precursors...
01:17Pore Transport and Ion-Pair Transport
Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct microscopic...
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct microscopic...
01:17Hormones and Bone Tissue
The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
01:09Multi-pass Transmembrane Proteins and β-barrels
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
01:34Nuclear Protein Sorting
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...