11,319 research outputs found
Introduction to protein folding for physicists
The prediction of the three-dimensional native structure of proteins from the
knowledge of their amino acid sequence, known as the protein folding problem,
is one of the most important yet unsolved issues of modern science. Since the
conformational behaviour of flexible molecules is nothing more than a complex
physical problem, increasingly more physicists are moving into the study of
protein systems, bringing with them powerful mathematical and computational
tools, as well as the sharp intuition and deep images inherent to the physics
discipline. This work attempts to facilitate the first steps of such a
transition. In order to achieve this goal, we provide an exhaustive account of
the reasons underlying the protein folding problem enormous relevance and
summarize the present-day status of the methods aimed to solving it. We also
provide an introduction to the particular structure of these biological
heteropolymers, and we physically define the problem stating the assumptions
behind this (commonly implicit) definition. Finally, we review the 'special
flavor' of statistical mechanics that is typically used to study the
astronomically large phase spaces of macromolecules. Throughout the whole work,
much material that is found scattered in the literature has been put together
here to improve comprehension and to serve as a handy reference.Comment: 53 pages, 18 figures, the figures are at a low resolution due to
arXiv restrictions, for high-res figures, go to http://www.pabloechenique.co
The bacterial antitoxin HipB establishes a ternary complex with operator DNA and phosphorylated toxin HipA to regulate bacterial persistence
Nearly all bacteria exhibit a type of phenotypic growth described as persistence that is thought to underlie antibiotic tolerance and recalcitrant chronic infections. The chromosomally encoded high-persistence (Hip) toxin-antitoxin proteins HipA(SO) and HipB(SO) from Shewanella oneidensis, a proteobacterium with unusual respiratory capacities, constitute a type II toxin-antitoxin protein module. Here we show that phosphorylated HipA(SO) can engage in an unexpected ternary complex with HipB(SO) and double-stranded operator DNA that is distinct from the prototypical counterpart complex from Escherichia coli. The structure of HipB(SO) in complex with operator DNA reveals a flexible C-terminus that is sequestered by HipA(SO) in the ternary complex, indicative of its role in binding HipA(SO) to abolish its function in persistence. The structure of HipA(SO) in complex with a non-hydrolyzable ATP analogue shows that HipA(SO) autophosphorylation is coupled to an unusual conformational change of its phosphorylation loop. However, HipA(SO) is unable to phosphorylate the translation factor Elongation factor Tu, contrary to previous reports, but in agreement with more recent findings. Our studies suggest that the phosphorylation state of HipA is an important factor in persistence and that the structural and mechanistic diversity of HipAB modules as regulatory factors in bacterial persistence is broader than previously thought
Ab initio RNA folding
RNA molecules are essential cellular machines performing a wide variety of
functions for which a specific three-dimensional structure is required. Over
the last several years, experimental determination of RNA structures through
X-ray crystallography and NMR seems to have reached a plateau in the number of
structures resolved each year, but as more and more RNA sequences are being
discovered, need for structure prediction tools to complement experimental data
is strong. Theoretical approaches to RNA folding have been developed since the
late nineties when the first algorithms for secondary structure prediction
appeared. Over the last 10 years a number of prediction methods for 3D
structures have been developed, first based on bioinformatics and data-mining,
and more recently based on a coarse-grained physical representation of the
systems. In this review we are going to present the challenges of RNA structure
prediction and the main ideas behind bioinformatic approaches and physics-based
approaches. We will focus on the description of the more recent physics-based
phenomenological models and on how they are built to include the specificity of
the interactions of RNA bases, whose role is critical in folding. Through
examples from different models, we will point out the strengths of
physics-based approaches, which are able not only to predict equilibrium
structures, but also to investigate dynamical and thermodynamical behavior, and
the open challenges to include more key interactions ruling RNA folding.Comment: 28 pages, 18 figure
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