Instruct: Identify the main and secondary category of Arxiv papers based on the titles and abstracts
Query: A dynamic intermediate state limits the folding rate of a discontinuous
  two-domain protein   Protein folding is an indispensable process for the majority of proteins
after their synthesis from ribosomes in the cell. Most in vitro protein folding
studies have focused on single-domain proteins. Hence, it is important to
understand the folding process of multi-domain proteins, especially when
domains are discontinuous. We choose the Maltose binding protein (MBP) as a
model system. In particular, we studied a mutant of MBP that folds slowly.
Here, using two- and three-color single-molecule Foerster resonance energy
transfer (smFRET) experiments, we study the refolding of both the domains and
the interaction between the domains of DM-MBP. Initial two-color smFRET
measurements of the N-terminal domain (NTD) reveal the presence of a folding
intermediate. The same folding intermediate is observed in measurements
monitoring the C- terminal domain (CTD) and the NTD-CTD (N-C) interface. The
refolding intermediate is dynamic on the sub-millisecond timescale.
Quantitative analysis on underlying dynamic interconversions revealed a delay
in NTD folding imposed by the entropic barrier being the primary cause for slow
DM-MBP folding. Moreover, CTD folds after NTD completes the folding. Using
three-color smFRET, we could show the NTD folds first and CTD later in a same
protein. Molecular dynamic simulations for temperature-induced unfolding on WT-
and DM-MBP identify a folding nucleus in the NTD, which is rich in hydrophobic
residues, and explains why the two mutations slow down the folding kinetics. In
the presence of the bacterial Hsp60 chaperonin system GroEL/ES, we observe that
DM-MBP is dynamic within the chaperonin cavity but the chaperonin limits the
conformational space of substrate. Hence, confinement aids DM-MBP in overcoming
the entropic barrier. The study reports on the subtle tuning and co-dependency
for protein folding between two-domains with a discontinuous arrangement.

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The categories of this paper are: comp-gas
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The categories of this paper are: acc-phys
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The categories of this paper are: solv-int
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The categories of this paper are: chem-ph
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The categories of this paper are: cond-mat
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The categories of this paper are: funct-an
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The categories of this paper are: supr-con
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The categories of this paper are: mtrl-th
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The categories of this paper are: dg-ga
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The categories of this paper are: cmp-lg
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The categories of this paper are: hep-ph
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The categories of this paper are: math
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The categories of this paper are: astro-ph
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The categories of this paper are: cs
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The categories of this paper are: hep-ex
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The categories of this paper are: gr-qc