VH Domains show larger Framework Struktural Variability than VL Domains

VH domains show larger structural variability than VL domains, as shown by the larger average core C-alpha rms deviation of close to 1Å compared to 0.5Å for VL domains (lambda and kappa).Much of this variability is correlated with the four conformational subtypes indicated by the identity of residues H6, a conserved glutamate or glutamine buried in the core of variable domain, and H9, which is usually proline, glycine or alanine. VL domain only have glutamine in position H9, TCR V-alpha and V-beta predominantly glutamin, but also some glutamate, VH domains approx. 50% Glu, 50% Gln.

The different hydrogen bondig patters of Glu and Gln seem to determine the kink in the main chain, its exact conformation being fine-tuned by the conformational flexibility of Residue H9, Gly and Pro in combination with Glu, Ala or Pro in combination with Gln. Sabine Jung produced all four combinations in the context of two different frameworks (aL2 and HAG) to prove that the relationship between local sequence and structure is a causal one.