The human PDI family: versatility packed into a single fold

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Protein disulfide isomerase (PDI) enzymes are thiol-disulfide oxidoreductases found in the endoplasmic reticulum (ER).
• PDIs feature a CXXC active-site motif essential for catalyzing disulfide bond exchange in substrates.
• The known functions of PDIs have expanded beyond oxidative protein folding to include ER-associated degradation (ERAD), trafficking, calcium homeostasis, antigen presentation, and virus entry.

Purpose of the Study:

• To explore the diverse cellular functions of human protein disulfide isomerase (PDI) family members.
• To emphasize the differences and similarities among human PDIs.
• To highlight the adaptability of the thioredoxin fold in various cellular processes.

Main Methods:

• Review and synthesis of existing literature on human PDI family functions.
• Analysis of structural homology to the thioredoxin fold across PDI members.
• Categorization of PDI functions based on cellular processes.

Main Results:

• Human PDIs exhibit a wide array of functions, including but not limited to oxidative protein folding.
• Some non-catalytic PDI members perform crucial roles despite lacking active-site cysteines.
• All human PDIs possess a domain structurally homologous to thioredoxin, underscoring the versatility of this fold.

Conclusions:

• The protein disulfide isomerase (PDI) family is more functionally diverse than previously understood.
• The thioredoxin fold provides a versatile structural basis for a multitude of cellular roles performed by PDIs.
• Understanding the distinct functions of individual PDIs is key to appreciating their complex cellular contributions.