Dataset Information

Probing protein mechanics: residue-level properties and their use in defining domains.

ABSTRACT: It is becoming clear that, in addition to structural properties, the mechanical properties of proteins can play an important role in their biological activity. It nevertheless remains difficult to probe these properties experimentally. Whereas single-molecule experiments give access to overall mechanical behavior, notably the impact of end-to-end stretching, it is currently impossible to directly obtain data on more local properties. We propose a theoretical method for probing the mechanical properties of protein structures at the single-amino acid level. This approach can be applied to both all-atom and simplified protein representations. The probing leads to force constants for local deformations and to deformation vectors indicating the paths of least mechanical resistance. It also reveals the mechanical coupling that exists between residues. Results obtained for a variety of proteins show that the calculated force constants vary over a wide range. An analysis of the induced deformations provides information that is distinct from that obtained with measures of atomic fluctuations and is more easily linked to residue-level properties than normal mode analyses or dynamic trajectories. It is also shown that the mechanical information obtained by residue-level probing opens a new route for defining so-called dynamical domains within protein structures.

SUBMITTER: Navizet I

PROVIDER: S-EPMC1304551 | biostudies-literature | 2004 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Probing protein mechanics: residue-level properties and their use in defining domains.

Navizet Isabelle I Cailliez Fabien F Lavery Richard R

Biophysical journal 20040901 3

It is becoming clear that, in addition to structural properties, the mechanical properties of proteins can play an important role in their biological activity. It nevertheless remains difficult to probe these properties experimentally. Whereas single-molecule experiments give access to overall mechanical behavior, notably the impact of end-to-end stretching, it is currently impossible to directly obtain data on more local properties. We propose a theoretical method for probing the mechanical pro ...[more]

PMID: 15345525

Similar Datasets

Project description:The atomic-level structural properties of proteins, such as bond lengths, bond angles, and torsion angles, have been well studied and understood based on either chemistry knowledge or statistical analysis. Similar properties on the residue-level, such as the distances between two residues and the angles formed by short sequences of residues, can be equally important for structural analysis and modeling, but these have not been examined and documented on a similar scale. While these properties are difficult to measure experimentally, they can be statistically estimated in meaningful ways based on their distributions in known proteins structures. Residue-level structural properties including various types of residue distances and angles are estimated statistically. A software package is built to provide direct access to the statistical data for the properties including some important correlations not previously investigated. The distributions of residue distances and angles may vary with varying sequences, but in most cases, are concentrated in some high probability ranges, corresponding to their frequent occurrences in either ?-helices or ?-sheets. Strong correlations among neighboring residue angles, similar to those between neighboring torsion angles at the atomic-level, are revealed based on their statistical measures. Residue-level statistical potentials can be defined using the statistical distributions and correlations of the residue distances and angles. Ramachandran-like plots for strongly correlated residue angles are plotted and analyzed. Their applications to structural evaluation and refinement are demonstrated. With the increase in both number and quality of known protein structures, many structural properties can be derived from sets of protein structures by statistical analysis and data mining, and these can even be used as a supplement to the experimental data for structure determinations. Indeed, the statistical measures on various types of residue distances and angles provide more systematic and quantitative assessments on these properties, which can otherwise be estimated only individually and qualitatively. Their distributions and correlations in known protein structures show their importance for providing insights into how proteins may fold naturally to various residue-level structures.

Project description:The endothelium has been established to generate intercellular stresses and suggested to transmit these intercellular stresses through cell-cell junctions, such as VE-Cadherin and ZO-1, for example. Although the previously mentioned molecules reflect the appreciable contributions both adherens junctions and tight junctions are believed to have in endothelial cell intercellular stresses, in doing so they also reveal the obscure relationship that exists between gap junctions and intercellular stresses. Therefore, to bring clarity to this relationship we disrupted expression of the endothelial gap junction connexin 43 (Cx43) by exposing confluent human umbilical vein endothelial cells (HUVECs) to a low (0.2 ?g/mL) and high (2 ?g/mL) concentration of 2,5-dihydroxychalcone (chalcone), a known Cx43 inhibitor. To evaluate the impact Cx43 disruption had on endothelial cell mechanics we utilized traction force microscopy and monolayer stress microscopy to measure cell-substrate tractions and cell-cell intercellular stresses, respectively. HUVEC monolayers exposed to a low concentration of chalcone produced average normal intercellular stresses that were on average 17% higher relative to control, while exposure to a high concentration of chalcone yielded average normal intercellular stresses that were on average 55% lower when compared to control HUVEC monolayers. HUVEC maximum shear intercellular stresses were observed to decrease by 16% (low chalcone concentration) and 66% (high chalcone concentration), while tractions exhibited an almost 2-fold decrease under high chalcone concentration. In addition, monolayer cell velocities were observed to decrease by 19% and 35% at low chalcone and high chalcone concentrations, respectively. Strain energies were also observed to decrease by 32% and 85% at low and high concentration of chalcone treatment, respectively, when compared to control. The findings we present here reveal for the first time the contribution Cx43 has to endothelial biomechanics.

Dataset Information

Probing protein mechanics: residue-level properties and their use in defining domains.

Publications

Probing protein mechanics: residue-level properties and their use in defining domains.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets