Affinity-stability trade-off mechanism of residue 35 in framework region 2 of V_HH antibodies with β-hairpin CDR3.

ABSTRACT: Single-domain V_HH antibodies are promising therapeutic and diagnostic tools. The third complementarity-determining region (CDR3) is usually the most critical region for antigen recognition by V_HH antibodies. When CDR3 adopts a short and extended β-hairpin conformation, framework region 2 (FR2) often interacts directly with the antigen. However, the importance of these interactions in antigen recognition remains unclear. In this research, we investigated the role of FR2 residues in V_HH antibodies with β-hairpin CDR3s. We found that several FR2 residues, particularly at positions 35 and 37, are critical for high-affinity antigen binding. Notably, a trade-off was observed: introducing a charged residue at position 35 enhanced binding affinity but reduced therm

SUBMITTER: Yamamoto K 

PROVIDER: S-EPMC11915348 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature