Determining the mechanism by which proteins attain their native structure is an important but difficult problem in basic biology. The study of protein folding is difficult because it involves the identification and characterization of folding intermediates that are only very transiently present. Disulfide bond formation is thermodynamically linked to protein folding. The availability of thiol t...

Both turn sequence and interstrand hydrophobic side-chain–sidechain interaction have been suggested to be important determinants of -hairpin stability. However, their roles in controlling the folding dynamics of -hairpins have not been clearly determined. Herein, we investigated the structural stability and folding kinetics of a series of tryptophan zippers by static IR and CD spectroscopies an...

Understanding the folding pattern of a single polymer chain within its single crystal will shed light on the mechanism of crystallization. Here, we use the combined techniques of atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) and steered molecular dynamics (SMD) simulations to study the folding pattern of a polyethylene oxide (PEO) chain in its single crystal. Our...

Subtilisin propeptide functions as an intramolecular chaperone that guides precursor folding. Nattokinase, a member of subtilisin family, is synthesized as a precursor consisting of a signal peptide, a propeptide, and a subtilisin domain, and the mechanism of its folding remains to be understood. In this study, the essential residues of nattokinase propeptide which contribute to precursor foldi...

How nascent polypeptides emerging from ribosomes fold into functional structures is poorly understood. Here, we monitor disulfide bond formation, protease resistance, and enzymatic activity in nascent polypeptides to show that in close proximity to the ribosome, conformational space and kinetics of folding are restricted. Folding constraints decrease incrementally with distance from the ribosom...

We propose a general theory to describe the distribution of protein-folding transition paths. We show that transition paths follow a predictable sequence of high-free-energy transient states that are separated by free-energy barriers. Each transient state corresponds to the assembly of one or more discrete, cooperative units, which are determined directly from the native structure. We show that...

A kinetic cluster method enables us to analyze biopolymer folding kinetics with discrete rate-limiting steps by classifying biopolymer conformations into pre-equilibrated clusters. The overall folding kinetics is determined by the intercluster transitions. Due to the complex energy landscapes of biopolymers, the intercluster transitions have multiple pathways and can have kinetic intermediates ...

We propose protein PTB1 : 4W as a good candidate for engineering into a downhill folder. PTB1 : 4W has a probe-dependent thermal unfolding curve and sub-millisecond T-jump relaxation kinetics on more than one time scale. Its refolding rate in denaturant is a non-linear function of denaturant concentration (curved chevron plot). Yet at high denaturant concentration its unfolding is probe-indepen...

BACKGROUND Kinase-inducible domain (KID) as transcriptional activator can stimulate target gene expression in signal transduction by associating with KID interacting domain (KIX). NMR spectra suggest that apo-KID is an unstructured protein. After post-translational modification by phosphorylation, KID undergoes a transition from disordered to well folded protein upon binding to KIX. However, th...