Related Experiment Video
Updated: Aug 13, 2025
15:04
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
6.0K
Nonspecific Amyloid Aggregation of Chicken Smooth-Muscle Titin: In Vitro Investigations
Alexander G Bobylev1, Elmira I Yakupova2, Liya G Bobyleva1
1Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, 142290 Moscow Region, Russia.
International Journal of Molecular Sciences
|January 21, 2023
Summary
Titin, a large muscle protein, forms amyloid aggregates in vitro without altering its secondary structure. These findings suggest specific protein regions drive aggregation, offering new insights into amyloidogenesis.
Area of Science:
- Biochemistry
- Structural Biology
- Muscle Physiology
Background:
- Titin is a giant multidomain protein found in vertebrate muscles, crucial for muscle structure and function.
- Titin comprises immunoglobulin (Ig) and fibronectin type III (FnIII) domains, forming β-sandwiches, alongside disordered segments.
- Chicken smooth muscles express various titin isoforms, with high-molecular-weight isoforms reaching approximately 1500 kDa.
Purpose of the Study:
- To investigate the in vitro amyloid aggregation of the high-molecular-weight isoform of chicken smooth-muscle titin (SMTHMW).
- To characterize the structural properties of SMTHMW amyloid aggregates under near-physiological conditions.
- To explore the potential role of specific titin domains or segments in the aggregation process.
Main Methods:
- X-ray diffraction analysis to confirm aggregate structure.
- Circular dichroism spectroscopy to assess secondary structure changes.
- Fourier-transform infrared spectroscopy to analyze protein structure.
- In vitro incubation under near-physiological conditions.
Main Results:
- SMTHMW formed amorphous amyloid aggregates with a cross-β structure within approximately 60 minutes.
- The formation of the cross-β structure occurred without significant changes in the secondary structure of SMTHMW.
- Increasing ionic strength above physiological levels led to partial disaggregation of SMTHMW aggregates.
- Evidence suggests specific domains or segments, not the entire protein, are involved in intermolecular interactions during aggregation.
Conclusions:
- Titin's unique amyloid aggregation properties, particularly the preservation of secondary structure, distinguish it from other amyloidogenic proteins.
- The findings indicate that specific regions of titin mediate its amyloid aggregation.
- SMTHMW serves as a valuable model for studying amyloid aggregation mechanisms in vitro and advancing our understanding of amyloidogenesis.
