Ligand binding variable domain (V-min) comprising a framework region with a cyclically permuted central beta-barrel

The invention relates to ligand binding variable domains (V-mins) having structural rearrangement of the binding domain of immunoglobulins and other Ligand binding members of the immunoglobulin superfamily. The minimal elements necessary to retain good antigen binding affinity, the complementarity determining region (CDRs) and the central beta barrel structure for the Fv fragment, may be retained positioned appropriately in space by cyclic permutation of the central beta barrel structure and leaving the strands of the beta -barrel intact. The invention is also independently based on recognising that after cyclic permutation of the central beta barrel the framework region which supports the CDRs can be pared down through creation of novel linkages in the structure.