Primary structure elements responsible for the conformational switch in the envelope glycoprotein gp120 from human immunodeficiency virus type 1: LPCR is a motif governing folding.
The ability to undergo a particular conformational switch on moving from a polar to a less polar environment has been shown to be conserved at the CD4-binding domain of the envelope glycoprotein gp120 from human immunodeficiency virus type 1 despite considerable variability in primary structure and is essential for the process of binding to the T-cell receptor CD4. The elements necessary to the expression of this behavior have been examined in synthetic peptides using circular dichroism and have been found to include a tetrad, LPCR, plus a tryptophan at a position 8 residues C-terminal to it. In the absence of the tryptophan the conformational change from beta-sheet to alpha-helix as medium polarity decreases does not occur abruptly but, rather, in a linear fashion. In the absence of the LPCR tetrad, no transition to alpha-helix occurs even at 100% trifluoroethanol. These two domains interact to control not only the beta-->alpha transition but also both its cooperativity and the critical point on the polar-->apolar gradient at which it occurs. Sequence similarity searches of the protein data banks suggest that an LPCR tetrad, governing the folding behavior of subsequent residues, may occur as a conserved motif in proteins in general. Synthetic peptides with the sequence of non-gp120 proteins that contain the tetrad do in fact display a similar pattern of folding response to decreasing polarity, with a sharp, cooperative transition from beta-sheet to alpha-helix. The LPCR tetrad appears to be a motif that controls secondary structure in a manner supplementary to that predicted by folding algorithms.
Reed
J
J
Department of Pathochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany.
Kinzel
V
V
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D013329:Structure-Activity Relationship
D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments