Solution NMR Determination of the CDHR3 Rhinovirus-C Binding Domain, EC1

Area of Science:

• Structural biology
• Virology
• Biochemistry

Background:

• Cadherin Related Family Member 3 (CDHR3) is the cellular receptor for all rhinovirus-C (RV-C) species.
• Previous cryo-EM studies resolved the structure of an RV-C15a virus-CDHR3 extracellular domain 1 (EC1) complex.

Purpose of the Study:

• To determine the structure of CDHR3 EC1 using solution NMR.
• To assess the structural flexibility of CDHR3 EC1 at the virus-binding interface.
• To identify structural features influencing RV-C binding and CDHR3 function.

Main Methods:

• Solution Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the structure of CDHR3 EC1.
• High-resolution structural data were analyzed to identify protein conformation and flexibility.
• Analysis focused on residues involved in calcium binding and potential protein-protein interactions.

Main Results:

• CDHR3 EC1 is largely inflexible, particularly at the virus-binding face.
• Three cis-Pro residues were identified in loop regions, influencing protein rigidity and conformation.
• The study clarified residues involved in calcium ion binding and revealed a potential surface groove for cellular interactions.

Conclusions:

• The structural rigidity of CDHR3 EC1 suggests a stable interaction with RV-C viruses.
• The identified cis-Pro residues and calcium-binding sites are critical for CDHR3 structure and function.
• The potential surface groove offers insights into CDHR3's native cellular interactions beyond viral binding.