Unusual amino acid sequence of the second Ig-like domain of the feline CD4 protein.
We have cloned and sequenced the cDNA for cat CD4. The overall amino-acid sequence of cat CD4 is similar to that from the primate and rodent CD4 molecules, with a 58% identity between the cat and human sequences. Comparison to the crystal structure of human CD4 does, however, reveal unusual features in the second Ig-like domain, D2, of cat CD4. First, a reciprocal substitution between a tryptophan and a cysteine, this latter involved in an intrasheet disulfide bond of human D2, is predicted to generate an intrastrand disulfide bond, a feature rarely observed in an Ig-fold. Second, a large serine-threonine-rich insertion is found between the A and B beta strands of D2. This sequence is a potential O-linked glycosylation site, and should protrude in a region that appears flexible in human CD4. This unusual insertion could affect the interaction of cat CD4 with class II molecules, or with FIV, a feline homolog of HIV. The expression of cat CD4 in different environment, or of a mutated human CD4 carrying the cat insertion, should help in understanding the role of cat CD4 as a putative receptor for FIV, and the CD4/MHC class II interaction.
Dumont-Drieux
A M
AM
Laboratoire de biologie et génétique des pathologies immunitaires, URA CNRS 1463-CERVI-Hôpital de la Pitié 83, Paris, France.
De Parseval
A
A
Heiber
M
M
Salmon
P
P
Pancino
G
G
Sonigo
P
P
Klatzmann
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000737:chemistry*; D002415:Cats; D003001:Cloning, Molecular; D003198:Computer Simulation; D004277:DNA, Single-Stranded; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D015704:CD4 Antigens; D004277:DNA, Single-Stranded; D007136:Immunoglobulins