Crystal structure of domains 3 and 4 of rat CD4: relation to the NH2-terminal domains
Brady RL, Dodson EJ, Dodson GG, Lange G, Davis SJ, Williams AF, Barclay AN. (1993), Science. 260, 979-83
The CD4 antigen is a membrane glycoprotein of T lymphocytes that interacts with major histocompatibility complex class II antigens and is also a receptor for the human immunodeficiency virus. the extracellular portion of CD4 is predicted to fold into four immunoglobulin-like domains. The crystal structure of the third and fourth domains of rat CD4 was solved at 2.8 angstrom resolution and shows that both domains have immunoglobulin folds. Domain 3, however, lacks the disulfide between the beta sheets; this results in an expansion of the domain. There is a difference of 30 degrees in the orientation between domains 3 and 4 when compared with domains 1 and 2. The two CD4 fragment structures provide a basis from which models of the overall receptor can be proposed. These models suggest an extended structure comprising two rigid portions joined by a short and possibly flexible linker region.
(A) Two orthogonal views of the crystallographic dimer formed by antiparallel H bonding of residues lle99, Leu100, and Tyr101 of strand G of D3. (B and C) Possible models, shown as a Cα trace, for the complete extracellular portion of CD4 comprising human D1 and D2 joined to rat D3 and D4 by simple interpolation of the five missing residues to complete strand G of D2 and strand A of D3. Rat and human CD4 have 55% overall sequence identity or 70% sequence similarity with most core structurally important residues being highly conserved and hence are likely to adopt very similar folds In (B), the connecting peptide (shown in pale green, with side chains in ideal conformations) joins the two fragments to bring conserved loop residues at the base of D2 into contact with the top of D3. The buried surface area between D2 and D3 in model (B) is approximately 600 Å2. The loop residues involved in the contacts are 107 through 111 and 150 through 154 in D2, and 18 through 26 and 93 through 98 in D3. Both models are approximately 120 Å in length.