Crystal structure of an extracellular fragment of the rat CD4 receptor containing domains 3 and 4.
BACKGROUND
CD4 is a transmembrane protein on the surface of T lymphocytes that interacts with MHC class II proteins at the surface of accessory cells, and is involved in the triggering of the lymphocytes by foreign antigens. It is also the major receptor for the human immunodeficiency virus. The extracellular portion of CD4 was predicted to contain four immunoglobulin superfamily domains and this has been confirmed by X-ray crystallography, but no detailed structure of domains 3 and 4 has been available.


RESULTS
We now report the expression of a form of rat CD4 containing only domains 3 and 4, its crystallization, and the refinement and analysis of its structure by X-ray crystallography with 2.6 A spacing data. Both domains show variations in core residues when compared with immunoglobulin domains. Features of the structure are discussed with respect to the structure of the complete extracellular part of CD4 and its function.


CONCLUSIONS
Domains 3 and 4 of CD4 show considerable similarity to domains 1 and 2, although there is a 25 degrees rotation in the relative positions of the domains with respect to one another. The absence of the disulphide bond in domain 3 is associated with an alteration in the packing of the beta-sheets, which may be important for interactions with domain 2 in the overall receptor structure. The location of N-linked glycosylation on one face of domain 3 appears to preclude the dimerization that is observed in antibodies.
Lange
G
G
Department of Chemistry, University of York, UK.
Lewis
S J
SJ
Murshudov
G N
GN
Dodson
G G
GG
Moody
P C
PC
Turkenburg
J P
JP
Barclay
A N
AN
Brady
R L
RL
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006031:Glycosylation; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008961:Models, Structural; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II