Structure and heterogeneity of a highly cargo-loaded encapsulin shell

Area of Science:

• Biochemistry
• Structural Biology
• Microbiology

Background:

• Encapsulins are self-assembling protein nanocompartments found in bacteria and archaea.
• They play roles in oxidative stress resistance, iron storage, and sulfur metabolism.
• Encapsulin shells have icosahedral symmetry and are composed of multiple protein subunits.

Approach:

• Reported the 2.53 Å cryo-electron microscopy (cryo-EM) structure of a T3 encapsulin shell from *Myxococcus xanthus*.
• Investigated structural heterogeneity in highly cargo-loaded encapsulin shells.
• Analyzed the binding mode of targeting peptides to the encapsulin shell interior.

Key Points:

• Exceedingly high cargo loading leads to distorted and aberrant shell formation.
• Steric clashes between cargo proteins and shell conformational changes likely cause these aberrations.
• Both ionic and hydrophobic interactions mediate the binding of targeting peptides to the encapsulin shell.

Conclusions:

• The determined structure provides insights into the targeting peptide-shell binding mechanism.
• Understanding these interactions is crucial for rationally engineering encapsulins.
• This research will guide future biomedical and biotechnological applications of encapsulins.