Spatial proximity between neighbouring strands implies main-chain hydrogen bonding. β-Strands are shown as arrows: black and labelled represent the 25 β-strands of core gp120 grey and unlabelled represent the continuation of hydrogen bonding across a sheet white and labelled represents the C″ strand of CD4. The diagram is arranged to coincide with the orientation of a, c, Helices are shown as corkscrews and labelled α1–α5. Selected parts of the structure are labelled. Connections are shown in grey, except for the disordered V4 loop (dashed line) connecting β18 and β19. α-Helices are depicted in red and β-strands in salmon, except for strand β15 (yellow), which makes an antiparallel β-sheet alignment with strand C″ of CD4. The bridging sheet (β3, β2, β21, β20) can be seen packing primarily over the inner domain, although some surface residues of the outer domain, such as Phe382, reach in to form part of its hydrophobic core. In this view, we describe the left portion of core gp120 as the inner domain, the right portion as the outer domain, and the 4-stranded sheet at the bottom left of gp120 as the bridging sheet. Thus the viral membrane would be oriented above, the target membrane below, and the C-terminal tail of CD4 would be coming out of the page. 1 by a 90° rotation about a vertical axis. In a–c, the orientation of gp120 is related to Fig. Our results provide a framework for understanding the complex biology of HIV entry into cells and should guide efforts to intervene. The structure reveals a cavity-laden CD4-gp120 interface, a conserved binding site for the chemokine receptor, evidence for a conformational change upon CD4 binding, the nature of a CD4-induced antibody epitope, and specific mechanisms for immune evasion. We have solved the X-ray crystal structure at 2.5 A resolution of an HIV-1 gp120 core complexed with a two-domain fragment of human CD4 and an antigen-binding fragment of a neutralizing antibody that blocks chemokine-receptor binding. Although gp120 can elicit virus-neutralizing antibodies, HIV eludes the immune system. These interactions initiate a fusion of the viral and cellular membranes. The entry of human immunodeficiency virus (HIV) into cells requires the sequential interaction of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |