Structural Flexibility and Shape Similarity Contribute to Exclusive Functions of Certain Atg8 Isoforms in the...

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Autophagy is a vital cellular process with many unknown aspects, including the selective interactions of autophagy-related protein (ATG8) isoforms with receptors in plants.
• These interactions are critical for regulating phagophore initiation, expansion, and maturation, controlling the assembly of autophagy proteins.

Purpose of the Study:

• To investigate the background selectivity of interactions between plant ATG8 isoforms and their receptors/adaptors.
• To understand the structural basis for differential selectivity among ATG8 isoforms during autophagy.

Main Methods:

• Bioinformatics analysis of ATG8 amino acid sequences from human, yeast, and plants to create a sequence tree.
• Structural studies and molecular dynamics (MD) simulations to analyze ATG8 isoform functionality and interactions.
• Root mean square deviation (RMSD)-based clustering analysis of the LIR docking site (LDS) interface.

Main Results:

• A sequence tree divided plant ATG8s into three groups, revealing conserved secondary structures and folding across all ATG8 proteins.
• MD simulations demonstrated stage-dependent functionality and significant binding preferences of ATG8-peptide complexes for specific partners among different ATG8 isotypes.
• Analysis identified conformational changes in adaptor and receptor contact regions during protein-peptide docking.

Conclusions:

• Despite conserved structures, ATG8 isoforms exhibit distinct selectivity for binding partners, which is essential for precise regulation of autophagy.
• Understanding these selective interactions provides insights into the complex mechanisms of autophagosome biogenesis and cargo recognition in plants.