16,907 research outputs found
Fibril elongation mechanisms of HET-s prion-forming domain: Topological evidence for growth polarity
The prion-forming C-terminal domain of the fungal prion HET-s forms
infectious amyloid fibrils at physiological pH. The conformational switch from
the non-prion soluble form to the prion fibrillar form is believed to have a
functional role, since HET-s in its prion form participates in a recognition
process of different fungal strains. Based on the knowledge of the
high-resolution structure of HET-s(218-289) (the prion forming-domain) in its
fibrillar form, we here present a numerical simulation of the fibril growth
process which emphasizes the role of the topological properties of the
fibrillar structure. An accurate thermodynamic analysis of the way an
intervening HET-s chain is recruited to the tip of the growing fibril suggests
that elongation proceeds through a dock and lock mechanism. First, the chain
docks onto the fibril by forming the longest -strands. Then, the
re-arrangement in the fibrillar form of all the rest of molecule takes place.
Interestingly, we predict also that one side of the HET-s fibril is more
suitable for substaining its growth with respect to the other. The resulting
strong polarity of fibril growth is a consequence of the complex topology of
HET-s fibrillar structure, since the central loop of the intervening chain
plays a crucially different role in favouring or not the attachment of the
C-terminus tail to the fibril, depending on the growth side.Comment: 16 pages, 10 figure
Enrichment and aggregation of topological motifs are independent organizational principles of integrated interaction networks
Topological network motifs represent functional relationships within and
between regulatory and protein-protein interaction networks. Enriched motifs
often aggregate into self-contained units forming functional modules.
Theoretical models for network evolution by duplication-divergence mechanisms
and for network topology by hierarchical scale-free networks have suggested a
one-to-one relation between network motif enrichment and aggregation, but this
relation has never been tested quantitatively in real biological interaction
networks. Here we introduce a novel method for assessing the statistical
significance of network motif aggregation and for identifying clusters of
overlapping network motifs. Using an integrated network of transcriptional,
posttranslational and protein-protein interactions in yeast we show that
network motif aggregation reflects a local modularity property which is
independent of network motif enrichment. In particular our method identified
novel functional network themes for a set of motifs which are not enriched yet
aggregate significantly and challenges the conventional view that network motif
enrichment is the most basic organizational principle of complex networks.Comment: 12 pages, 5 figure
Toward a multilevel representation of protein molecules: comparative approaches to the aggregation/folding propensity problem
This paper builds upon the fundamental work of Niwa et al. [34], which
provides the unique possibility to analyze the relative aggregation/folding
propensity of the elements of the entire Escherichia coli (E. coli) proteome in
a cell-free standardized microenvironment. The hardness of the problem comes
from the superposition between the driving forces of intra- and inter-molecule
interactions and it is mirrored by the evidences of shift from folding to
aggregation phenotypes by single-point mutations [10]. Here we apply several
state-of-the-art classification methods coming from the field of structural
pattern recognition, with the aim to compare different representations of the
same proteins gathered from the Niwa et al. data base; such representations
include sequences and labeled (contact) graphs enriched with chemico-physical
attributes. By this comparison, we are able to identify also some interesting
general properties of proteins. Notably, (i) we suggest a threshold around 250
residues discriminating "easily foldable" from "hardly foldable" molecules
consistent with other independent experiments, and (ii) we highlight the
relevance of contact graph spectra for folding behavior discrimination and
characterization of the E. coli solubility data. The soundness of the
experimental results presented in this paper is proved by the statistically
relevant relationships discovered among the chemico-physical description of
proteins and the developed cost matrix of substitution used in the various
discrimination systems.Comment: 17 pages, 3 figures, 46 reference
Decoding the urban grid: or why cities are neither trees nor perfect grids
In a previous paper (Figueiredo and Amorim, 2005), we introduced the continuity
lines, a compressed description that encapsulates topological and geometrical
properties of urban grids. In this paper, we applied this technique to a large
database of maps that included cities of 22 countries. We explore how this
representation encodes into networks universal features of urban grids and, at the
same time, retrieves differences that reflect classes of cities. Then, we propose an
emergent taxonomy for urban grids
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