title: Calmodulin-binding function of LLP segments from the HIV type 1 transmembrane protein is conserved among natural sequence variants.
abstract: LLP1 is a peptide, derived from the cytoplasmic tail of HIV-1 TM glycoprotein, that binds and inhibits calmodulin; this region is generally conserved among isolates, but amino acid variation does exist both within clade B and among different clades, as well as SIV. In light of previous studies showing that selected single amino acid changes can have a qualitatively significant effect on the calmodulin-binding properties of this peptide, we sought to examine the properties of naturally occurring variant LLP1 sequences. Using a quantitative fluorescence-based method to measure dissociation constants of calmodulin-LLP1 complexes, a remarkable conservation of calmodulin-binding function among natural variants was revealed. In contrast, engineered nonconservative single amino acid changes altered the affinity of the peptide for calmodulin. The results show that the calmodulin-binding function is well preserved despite the sequence variation observed in nature, suggesting that this region of the TM protein is important to viral replication.
authors.affiliation: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Tencza
authors.forename: T A
authors.initials: TA
authors.lastname: Mietzner
authors.forename: R C
authors.initials: RC
authors.lastname: Montelaro
mesh_terms: D000595:Amino Acid Sequence; D002147:Calmodulin / Q000378:metabolism*; D003619:Dansyl Compounds / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D002147:Calmodulin; D003619:Dansyl Compounds; D015700:HIV Envelope Protein gp41; D010455:Peptides