Instruct: Identify the main and secondary category of Arxiv papers based on the titles and abstracts
Query: An internal disulfide locks a misfolded aggregation-prone intermediate
  in cataract-linked mutants of human {\gamma}D-crystallin   Considerable mechanistic insight has been gained into amyloid aggregation;
however, a large class of non-amyloid protein aggregates are considered
'amorphous,' and in most cases little is known about their mechanisms.
Amorphous aggregation of {\gamma}-crystallins in the eye lens causes a
widespread disease of aging, cataract. We combined simulations and experiments
to study the mechanism of aggregation of two {\gamma}D-crystallin mutants, W42R
and W42Q - the former a congenital cataract mutation, and the latter a mimic of
age-related oxidative damage. We found that formation of an internal disulfide
was necessary and sufficient for aggregation under physiological conditions.
Two-chain all-atom simulations predicted that one non-native disulfide in
particular, between Cys32 and Cys41, was likely to stabilize an unfolding
intermediate prone to intermolecular interactions. Mass spectrometry and
mutagenesis experiments confirmed the presence of this bond in the aggregates
and its necessity for oxidative aggregation under physiological conditions in
vitro. Mining the simulation data linked formation of this disulfide to
extrusion of the N-terminal \b{eta}-hairpin and rearrangement of the native
\b{eta}-sheet topology. Specific binding between the extruded hairpin and a
distal \b{eta}-sheet, in an intermolecular chain reaction similar to domain
swapping, is the most probable mechanism of aggregate propagation.

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The categories of this paper are: quant-ph
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The categories of this paper are: patt-sol
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The categories of this paper are: q-fin
2
The categories of this paper are: math
8
The categories of this paper are: hep-ex
35
The categories of this paper are: mtrl-th
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The categories of this paper are: stat
33
The categories of this paper are: plasm-ph
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The categories of this paper are: comp-gas
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The categories of this paper are: alg-geom
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The categories of this paper are: astro-ph
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The categories of this paper are: gr-qc
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The categories of this paper are: atom-ph
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The categories of this paper are: dg-ga
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The categories of this paper are: hep-th
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The categories of this paper are: eess