STRUCTURE OF THE FAB FRAGMENT FROM A NEUTRALIZING MONOCLONAL-ANTIBODYDIRECTED AGAINST AN EPITOPE OF GP41 FROM HIV-1

The structure of a Fab fragment of a monoclonal antibody (1583) that n eutralizes a broad range of HIV-1 isolates has been solved by X-ray cr ystallography. This antibody is directed against a poliovirus/HIV-1 ch imaera which presents a conserved epitope of the envelope protein gp41 . Crystals of 1583 were obtained in the space group P2(1)2(1)2(1) and the structure solved by molecular replacement. The model has been refi ned against all data in the range 10-2.9 Angstrom to a final crystallo graphic R factor of 0.198. The antigen-binding site features a well de fined groove, typical of antibodies that bind to small antigens, creat ed in part by a relatively short CDR H3. The variable regions of 1583 were sequenced and, given the hydrophilic nature of the epitope, revea led a surprising lack of charged residues in the CDR's. However, the a ntigen-binding cleft is indeed very polar, due in part to the presence of two charged residues that emanate from outside the recognised CDR' s.