title: Refinement and analysis of the structure of the first two domains of human CD4.
abstract: The structure of a fragment of human CD4 containing two immunoglobulin (Ig)-like domains has been determined by X-ray crystallography and refined at 2.2 A resolution. The structure determination involved iterative building and simulated-annealing refinement, beginning with a partial model. Comparison of domain 1 with an Ig variable domain shows that CD4 has a long and prominent CDR2-like loop (the C"C" corner) and shortened CC' and FG loops (which mediate dimerization in IgV modules). Comparison of domain 2 with Ig modules and domain 1 shows that it can be described as a truncated Ig V domain, in which strands C" and D are deleted. The intersheet disulfide in domain 2 is absent, and there is an altered packing of the two beta-sheets together with a remodeling of the hydrophobic core. The interface between domains 1 and 2 is a lap joint with an extensive hydrophobic surface. The key features of domain 1 that contribute to the interface are found at corresponding positions in domain 2, leading us to propose that the contact between domains 2 and 3 will resemble the one between domains 1 and 2.
authors.affiliation: Howard Hughes Medical Institute, Cambridge, MA.
authors.forename: T P
authors.initials: TP
authors.lastname: Garrett
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Yan
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: S C
authors.initials: SC
authors.lastname: Harrison
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry*; D015704:CD4 Antigens / Q000737:chemistry*; D018360:Crystallography, X-Ray / Q000379:methods; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007147:Immunoglobulin Light Chains / Q000737:chemistry; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry; D007136:Immunoglobulins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D007140:Immunoglobulin Fab Fragments; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007136:Immunoglobulins; D010446:Peptide Fragments