Open AccessSimulation of Top7-CFr: A transient helix extension guides folding
Author(s) -
Sandipan Mohanty,
Jan H. Meinke,
Olav Zimmermann,
Ulrich H. E. Hansmann
Publication year - 2008
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0708411105
Subject(s) - folding (dsp implementation) , protein folding , sequence (biology) , beta (programming language) , beta sheet , biophysics , chemistry , peptide sequence , n terminus , terminal (telecommunication) , protein structure , computational biology , crystallography , computer science , biology , biochemistry , gene , telecommunications , electrical engineering , engineering , programming language
Protein structures often feature beta-sheets in which adjacent beta-strands have large sequence separation. How the folding process orchestrates the formation and correct arrangement of these strands is not comprehensively understood. Particularly challenging are proteins in which beta-strands at the N and C termini are neighbors in a beta-sheet. The N-terminal beta-strand is synthesized early on, but it can not bind to the C terminus before the chain is fully synthesized. During this time, there is a danger that the beta-strand at the N terminus interacts with nearby molecules, leading to potentially harmful aggregates of incompletely folded proteins. Simulations of the C-terminal fragment of Top7 show that this risk of misfolding and aggregation can be avoided by a "caching" mechanism that relies on the "chameleon" behavior of certain segments.