Structural basis of oligomerization in the stalk region of dynamin-like MxA

Area of Science:

• Structural biology
• Immunology
• Virology

Background:

• Myxovirus resistance protein 1 (MxA) is vital for innate immunity against viral infections.
• MxA functions by interfering with viral replication, partly through missorting viral components.
• The oligomerization mechanism of MxA, particularly its stalk region, remained structurally undefined.

Purpose of the Study:

• To determine the crystal structure of the MxA stalk domain.
• To elucidate the molecular architecture and oligomerization interfaces of the MxA stalk.
• To understand the functional implications of MxA stalk structure on its antiviral activity.

Main Methods:

• X-ray crystallography was used to determine the structure of the human MxA stalk.
• Mutagenesis studies were performed to analyze the function of identified interaction sites.
• Oligomerization, membrane binding, and antiviral activity assays were conducted.

Main Results:

• The MxA stalk adopts a four-helical bundle structure.
• This bundle undergoes tight oligomerization in a criss-cross manner via three interfaces and one loop.
• Mutations in these interaction sites disrupt MxA assembly, oligomerization, membrane binding, and antiviral function.

Conclusions:

• The determined MxA stalk structure provides a molecular basis for dynamin oligomerization.
• This structure offers insights into how conformational changes are transmitted for GTPase activity.
• The findings have implications for understanding the broader dynamin protein family and developing antiviral strategies.