Apomyoglobin sequesters heme from heme bound Aβ peptides

Area of Science:

• Biochemistry
• Spectroscopy
• Protein-heme interactions

Background:

• Amyloid beta (Aβ) can bind heme, forming heme-Aβ complexes.
• These complexes may contribute to oxidative stress through reactive oxygen species (ROS) generation.
• Apomyoglobin (apoMb) is a heme-free protein that can bind heme.

Purpose of the Study:

• To investigate the interaction between heme-Aβ and apoMb.
• To determine if apoMb can sequester heme from heme-Aβ complexes.
• To assess the impact of heme transfer on ROS generation.

Main Methods:

• Absorption spectroscopy to monitor spectral changes.
• Electron paramagnetic resonance (EPR) spectroscopy.
• Resonance Raman (rR) spectroscopy to analyze heme vibrational modes.

Main Results:

• Spectroscopic analysis confirmed heme transfer from heme-Aβ to apoMb, forming functional myoglobin (Mb) and deoxyMb.
• Heme uptake followed biphasic kinetics, suggesting heme transfer from distinct heme-Aβ conformers.
• Heme sequestration by apoMb significantly reduced ROS production by reduced heme-Aβ.

Conclusions:

• ApoMb efficiently sequesters heme from both oxidized and reduced heme-Aβ complexes.
• The heme transfer process is kinetically characterized by two distinct phases.
• ApoMb-mediated heme sequestration mitigates oxidative stress associated with heme-Aβ.