Refinement and Analysis of the Structure of the First Two Domains of Human CD4

The crystal structure of an N-terminal two-domain fragment of vascular cell adhesion molecule 1 (VCAM-1): a cyclic peptide based on the domain 1 C-D loop can inhibit VCAM-1-alpha 4 integrin interaction.

“…The total buried surface area, as calculated with ACCESS is 800 A2. This area is smaller than that in CD4-D1D2 [1100 A2 (29)] but larger than that in CD2 [400 A2 (25)]. As shown in Fig.…”

Localization of the Binding Site on Intercellular Adhesion Molecule-3 (ICAM-3) for Lymphocyte Function-associated Antigen 1 (LFA-1)

“…In contrast, complete deletion of domain 1 of ICAM-3 or point mutations that caused loss of all epitopes in domain 1 of ICAM-3 did not affect the expression of domain 2 epitopes. Nevertheless, domains 1 and 2 of ICAM-3 are predicted to be closely associated, as shown for other adhesion molecules with IgSF domains, CD4 (35) and CD2 (36). Indeed, two ICAM-3 mAb, KS128 and 152-2D11, required the presence of both ICAM-3 domains 1 and 2, which suggests an epitope that spans both domains.…”

“…This is in contrast to human VCAM-1, where Gln 38 , Asp 40 , and Leu 43 were individually shown to be important for transfected COS binding to VLA-4 on Ramos cells, and a 5-residue consensus sequence was proposed to be important for integrin binding (23). This was subsequently proven when a peptide encompassing VCAM-1 residues Trp 35 -Lys 46 was shown to block binding of Ramos cells to purified, recombinant soluble VCAM-1 on plastic (37). Similarly, a synthetic peptide from the corresponding region of ICAM-2 has been shown to bind LFA-1, whereas the corresponding region from ICAM-1 or ICAM-3 did not bind (19).…”

Structure of an HIV-2 gp120 in Complex with CD4

“…Conversely, HIV-2 gp120 has CD4 interactions that do not occur in HIV-1: loop D residue R293 gp120-ST interacts with E87 CD4 and D88 CD4 . Also, the BC loop of CD4 (residues 19 to 25), which in other CD4 structures (11,20,36) (including structures of CD4 alone [41][42][43]) is packed against the CD4 DE loop, is displaced ϳ6 Å toward HIV-2 gp120, interacting with E84 gp120-ST and N79 gp120-ST near the beginning of the ␣1 helix.…”