Effect of variation of the strength of the aromatic interactions of tryptophan on the cooperative structural refolding behavior of a peptide from HIV 1
Simon Schweizer 1 and Jennifer Reed 1*
1 German Cancer Research Center
* To whom correspondence should be addressed. E-mail: j.reed{at}dkfz-heidelberg.de.
Submitted on January 25, 2008
Revised on February 24, 2008
Accepted on 27 May 2008
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Abstract |
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A 15-residue sequence (LPCRIKQFINMWQEV) forming the principal CD4-binding domain of gp120 from HIV 1 displays unusual, highly cooperative re-folding from beta hairpin to 3-10 helix when the polarity of the surrounding medium drops below a critical point, the so-called conformational switch. The tryptophan at position 12 has been shown to be essential for the cooperativity of the re-folding process, and several lines of evidence from earlier work had suggested that it was the aromatic quadrupole that was responsible for this. In order to define more precisely what physico-chemical properties of tryptophan brought about the unique behaviour of this peptide, non-proteogenic aromatic amino acids have been selected based on desired alterations in quadrupole moment, electrostatic potential surface and binding energy to ions. These were built into the peptide in the place of tryptophan and their effect on switch behaviour examined. It could be shown that a minimal strength of the quadrupole moment is necessary but not sufficient to enforce cooperativity of refolding, with other properties of tryptophan playing a role in the optimum interaction of this residue with other side chains of the peptide.
Key Words:
aromatic interactions, circular dichroism, gp120, peptide, quadrupole, tryptophan
