Crossection of the VL domain showing the hydrogen bonding pattern of Gln L6

pink: VL lambda, purple: VL kappa. Observe fourth hydrogen bond to conserved buried Thr side chain OH, which also hydrogen bonds to the main chain cis-prolin L8

Stefania Spada, SIP-results, showed that despite folding kinetics, cis-pro in L8 is consistently selected overa library of alternative sequences (L7-L8), including the 1AA deletion seen on VL lambda and heavy chains

It is possible that the intricate conserved hydrogen bonding pattern of polar side chains in the core of immunoglobulin variable domain help these domains to prevent misfolding induced by the variability of the complementary determining regions, although at cost of thermodynamic stability. In that respect, it would be interesting to measure and compare the stabilties of constant domains to those of variable domains.