Different chains for different gains: How acyl chain diversity shapes S-acylated protein function

Area of Science:

• Biochemistry and Molecular Biology
• Post-Translational Modifications
• Lipid Biology

Background:

• S-acylation is a crucial post-translational modification attaching fatty acyl chains to proteins.
• Recent advances include discovering acylation enzymes and mapping the cellular S-acylome.
• Chemical biology tools have enhanced understanding of S-acylation mechanisms and functions.

Purpose of the Study:

• To highlight the diversity of acyl chains involved in S-acylation beyond palmitate.
• To emphasize the importance of acyl chain heterogeneity in protein regulation.
• To underscore the need for further research into the functional consequences of this diversity.

Main Methods:

• Mass spectrometry analyses to identify and characterize acyl chains on S-acylated proteins.
• Investigation of enzyme specificities and Acyl CoA availability.
• Analysis of substrate protein features influencing modification.

Main Results:

• Mass spectrometry data confirm diverse acyl chains, not just palmitate, are attached to proteins.
• Evidence shows site-specific attachment of different acyl chains.
• Exogenous fatty acids can alter the S-acylome's lipid profile.

Conclusions:

• S-acylation exhibits significant acyl chain heterogeneity, impacting protein localization and function.
• This diversity, influenced by enzymes, Acyl CoA, and substrate proteins, is critical for lipid-mediated protein regulation.
• Recognizing acyl chain differences is essential for a complete understanding of protein regulation and potential disease links.