Solution structure and dynamics of the central CCP module pair of a poxvirus complement control protein

Area of Science:

• Structural Biology
• Biochemistry
• Immunology

Background:

• Complement control protein (CCP) modules regulate complement activation.
• The spatial orientation and flexibility of CCP modules are crucial for function.
• Previous studies solved the structure of VCP CCP modules 3 and 4.

Purpose of the Study:

• To determine the solution structure of VCP CCP modules 2 and 3 (VCP approximately 2,3).
• To characterize the backbone dynamics of VCP approximately 2,3.
• To understand the intermodular interactions and their impact on VCP structure and function.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy at 37°C.
• Analysis of (15)N relaxation parameters for backbone dynamics.
• Structure calculation based on Nuclear Overhauser Effect (NOE) data.

Main Results:

• Module 2 exhibits a typical CCP structure; Module 3 shows modest structural and dynamic differences compared to the 3,4 pair.
• Modules 2 and 3 interact primarily through the intermodular linker, favoring an elongated orientation.
• Dynamics data suggest multiple intermodular orientations and flexibility on the 10(-8)-10(-6) second timescale.

Conclusions:

• The VCP approximately 2,3 structure reveals a preferred, elongated conformation driven by linker interactions.
• Significant flexibility exists between CCP modules 2 and 3, influencing overall protein dynamics.
• Understanding VCP structure-dynamics is vital for interpreting its role in complement regulation and viral immune evasion.