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A strained DNA binding helix is conserved for site recognition, folding nucleation, and conformational modulation
Author(s) -
Wetzler Diana E.,
Gallo Mariana,
Melis Riccardo,
Eliseo Tomasso,
Nadra Alejandro D.,
Ferreiro Diego U.,
Paci Maurizio,
Sánchez Ignacio E.,
Cicero Daniel O.,
de Prat Gay Gonzalo
Publication year - 2009
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21146
Subject(s) - chemistry , helix (gastropod) , polyproline helix , crystallography , triple helix , helix turn helix , folding (dsp implementation) , dna , peptide , stereochemistry , turn (biochemistry) , biophysics , dna binding protein , biochemistry , transcription factor , biology , ecology , snail , gene , electrical engineering , engineering
Nucleic acid recognition is often mediated by α‐helices or disordered regions that fold into α‐helix on binding. A peptide bearing the DNA recognition helix of HPV16 E2 displays type II polyproline (PII) structure as judged by pH, temperature, and solvent effects on the CD spectra. NMR experiments indicate that the canonical α‐helix is stabilized at the N‐terminus, while the PII forms at the C‐terminus half of the peptide. Re‐examination of the dihedral angles of the DNA binding helix in the crystal structure and analysis of the NMR chemical shift indexes confirm that the N‐terminus half is a canonical α‐helix, while the C‐terminal half adopts a 3 10 helix structure. These regions precisely match two locally driven folding nucleii, which partake in the native hydrophobic core and modulate a conformational switch in the DNA binding helix. The peptide shows only weak and unspecific residual DNA binding, 10 4 ‐fold lower affinity, and 500‐fold lower discrimination capacity compared with the domain. Thus, the precise side chain conformation required for modulated and tight physiological binding by HPV E2 is largely determined by the noncanonical strained α‐helix conformation, “presented” by this unique architecture. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 432–443, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com