  The VHHs are antigen-binding region/domain of camelid heavy chain antibodies
(HCAb). They have many interesting biotechnological and biomedical properties
due to their small size, high solubility and stability, and high affinity and
specificity for their antigens. HCAb and classical IgGs are evolutionary
related and share a common fold. VHHs are composed of regions considered as
constant, called the frameworks (FRs) connected by Complementarity Determining
Regions (CDRs), a highly variable region that provide interaction with the
epitope. Actually, no systematic structural analyses had been performed on VHH
structures despite a significant number of structures. This work is the first
study to analyse the structural diversity of FRs of VHHs. Using a structural
alphabet that allows approximating the local conformation, we show that each of
the four FRs do not have a unique structure but exhibit many structural variant
patterns. Moreover, no direct simple link between the local conformational
change and amino acid composition can be detected. These results indicate that
long-range interactions affect the local conformation of FRs and impact the
building of structural models.
