Diverse crystalline protein scaffolds through metal-dependent polymorphism

Area of Science:

• Biomaterials Science
• Crystallography
• Protein Engineering

Background:

• Protein crystals are emerging as versatile scaffolds for advanced applications.
• Controlling crystal polymorphism is key to tailoring material properties like porosity.
• Minimal protein engineering is desired for facile scaffold development.

Purpose of the Study:

• To investigate controlled crystal polymorphism in proteins using metal ion coordination.
• To create protein assemblies with tunable porosity.
• To explore the application of these protein crystals as biocompatible protein-metal-organic frameworks (POFs).

Main Methods:

• Co-crystallization of consensus tetratricopeptide repeat proteins with various metal salts.
• Utilizing innate metal ion geometric requirements for coordination.
• Employing Density Functional Theory (DFT) calculations to analyze crystal stability and formation pathways.

Main Results:

• Achieved varying degrees of porosity in protein crystals through metal salt co-crystallization.
• Identified a specific, structurally exposed negative amino acid cluster responsible for metal coordination.
• DFT calculations revealed that some crystal polymorphs represent kinetically trapped states, while others are thermodynamically stable.

Conclusions:

• Metal coordination provides a facile and effective strategy to control protein crystal polymorphism and porosity.
• This approach enables the development of biocompatible protein-metal-organic frameworks (POFs) with tunable properties.
• Metal-dependent polymorphic crystals offer a platform for studying metal coordination preferences in proteins.