Details

Autor(en) / Beteiligte

• Lindberg, Magnus O.
• Haglund, Ellinor
• Hubner, Isaac A.
• Shakhnovich, Eugene I.
• Oliveberg, Mikael

Titel

Identification of the Minimal Protein-Folding Nucleus through Loop-Entropy Perturbations

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2006-03, Vol.103 (11), p.4083-4088

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2006

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• To explore the plasticity and structural constraints of the proteinfolding nucleus we have constructed through circular permutation four topological variants of the ribosomal protein S6. In effect, these topological variants represent entropy mutants with maintained spatial contacts. The proteins were characterized at two complementary levels of detail: by ø-value analysis estimating the extent of contact formation in the transition-state ensemble and by Hammond analysis measuring the site-specific growth of the folding nucleus. The results show that, although the loop-entropy alterations markedly influence the appearance and structural location of the folding nucleus, it retains a common motif of one helix docking against two strands. This nucleation motif is built around a shared subset of side chains in the center of the hydrophobic core but extends in different directions of the S6 structure following the permutant-specific differences in local loop entropies. The adjustment of the critical folding nucleus to alterations in loop entropies is reflected by a direct correlation between the ϕ-value change and the accompanying change in local sequence separation.