CALMODULIN-BINDING FUNCTION OF LLP SEGMENTS FROM THE HIV TYPE-1 TRANSMEMBRANE PROTEIN IS CONSERVED AMONG NATURAL SEQUENCE VARIANTS

LLP1 is a peptide, derived from the cytoplasmic tail of HIV-1 TM glyco protein, that binds and inhibits calmodulin; this region is generally conserved among isolates, but amino acid variation does exist both wit hin clade B and among different clades, as well as SIV, In light of pr evious studies showing that selected single amino acid changes can hav e a qualitatively significant effect on the calmodulin-binding propert ies of this peptide, we sought to examine the properties of naturally occurring variant LLP1 sequences, Using a quantitative fluorescence-ba sed method to measure dissociation constants of calmodulin-LLP1 comple xes, a remarkable conservation of calmodulin-binding function among na tural variants was revealed, In contrast, engineered nonconservative s ingle amino acid changes altered the affinity of the peptide for calmo dulin, The results show that the calmodulin-binding function is well p reserved despite the sequence variation observed in nature, suggesting that this region of the TM protein is important to viral replication.