Binding Studies of a Triple-Helical Peptide Model of Macrophage Scavenger Receptor to Tetraplex Nucleic Acids

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• 作者：Slawomir S. Mielewczyk and ; Kenneth J. Breslauer ; Rajini Balakrishnan Anachi ; and Barbara Brodsky
• 刊名：Biochemistry
• 出版年：1996
• 出版时间：September 3, 1996
• 年：1996
• 卷：35
• 期：35
• 页码：11396 - 11402
• 全文大小：381K
• 年卷期：v.35,no.35(September 3, 1996)
• ISSN：1520-4995

文摘

The macrophage scavenger receptor (MSR), involved in the uptake ofoxidized LDL, binds avariety of polyanionic ligands, and in particular shows selectivity fortetraplex forms of nucleic acids.The ligand binding region has been shown to lie in thetriple-helical collagen-like domain of MSR. Amodel peptide-nucleic acid system is presented here to clarify howthe triple-helical motif of MSRrecognizes and binds tetraplex nucleic acids. The triple-helicalpeptide MSR-1, with the sequence(POG)₃PKGQKGEKG(POG)₄, contains a nineamino acid basic sequence implicated in MSR ligandbinding, flanked by Pro-Hyp-Gly triplets to provide stability. Theability of this triple-helical MSR-1peptide to bind to and perturb the conformation of nucleic acids intetraplex, duplex, and single-strandedstates was assessed by monitoring changes in the nucleic acid circulardichroism spectrum in the 240-300 nm region. Our results show that the triple-helical MSR-1peptide binds to tetraplex poly(I) in astoichiometric manner and is capable of reproducing the discriminationexhibited by the native MSRmolecule for tetraplex over double-stranded or single-stranded nucleicacid states. The triple-helicalreference peptide (POG)₁₀ does not bind to tetraplexpoly(I), suggesting that binding requires the highlybasic 9-mer sequence from MSR that is included in MSR-1. The MSR-1peptide did not perturb the CDspectra of a series of other tetraplex nucleic acids, indicating thatit does not model the broader specificitythat MSR shows under physiological conditions. Models of possibleinteractions between a triple-helicalpeptide and a tetraplex polynucleotide are proposed on the basis of thestoichiometry observed for thecomplex between triple-helical MSR-1 and tetraplexpoly(I).