beta1- and beta2-adrenoceptor induced synaptic facilitation in rat basolateral amygdala.

The expression and characteristics of beta-adrenoceptor subtypes (beta1 and beta2) and their agonist actions on synaptic transmission in the basolateral amygdala (BLA) of the rat were examined using in situ hybridization, quantitative real-time PCR, Western blot analysis and field potential recording. In situ hybridization data revealed an intense distribution of beta1-and beta2-adrenoceptor mRNA in the BLA. Real-time PCR analysis of rat amygdala revealed significant transcriptional expression levels of both beta-adrenoceptors, with beta2-adrenoceptors outnumbering beta1-adrenoceptors in a ratio of 2.9 to 1. Bath application of the selective beta1-adrenoceptor agonist xamoterol hemifumarate (10 microM) facilitated the excitatory field synaptic potential evoked in the BLA by stimulation of the external capsule by 186.5+/-10.7% of control amplitude. In the presence of the selective beta1-adrenoceptor antagonist betaxolol hydrochloride (30 microM), the facilitating effects of field excitatory synaptic potential induced by the agonist were reduced to 126.1+/-2.3 % of control amplitude in the BLA. Bath application of the selective beta2-adrenoceptor agonist salmeterol (15 microM) facilitated the excitatory field synaptic potential evoked in the BLA by stimulation of the external capsule by 167.3+/-9.7 % of control amplitude. In the presence of the selective beta2-adrenoceptor antagonist ICI 118,551 HCl (30 microM), the facilitating effects of field excitatory synaptic potential induced by the agonist were reduced to 121.1+/-4.1 % of control amplitude in the BLA. These data suggest that beta-adrenoceptor mediated synaptic facilitation in the amygdala is mediated by both beta1 and beta2-adrenoceptor activation.

The Database of Macromolecular Motions: new features added at the decade mark.

The database of molecular motions, MolMovDB (http://molmovdb.org), has been in existence for the past decade. It classifies macromolecular motions and provides tools to interpolate between two conformations (the Morph Server) and predict possible motions in a single structure. In 2005, we expanded the services offered on MolMovDB. In particular, we further developed the Morph Server to produce improved interpolations between two submitted structures. We added support for multiple chains to the original adiabatic mapping interpolation, allowing the analysis of subunit motions. We also added the option of using FRODA interpolation, which allows for more complex pathways, potentially overcoming steric barriers. We added an interface to a hinge prediction service, which acts on single structures and predicts likely residue points for flexibility. We developed tools to relate such points of flexibility in a structure to particular key residue positions, i.e. active sites or highly conserved positions. Lastly, we began relating our motion classification scheme to function using descriptions from the Gene Ontology Consortium.

PARE: a tool for comparing protein abundance and mRNA expression data.

BACKGROUND: Techniques for measuring protein abundance are rapidly advancing and we are now in a situation where we anticipate many protein abundance data sets will be available in the near future. Since proteins are translated from mRNAs, their expression is expected to be related to their abundance, to some degree. RESULTS: We have developed a web tool, called PARE (Protein Abundance and mRNA Expression; http://proteomics.gersteinlab.org), to correlate these two quantities. In addition to globally comparing the quantities of protein and mRNA, PARE allows users to select subsets of proteins for focused study (based on functional categories and complexes). Furthermore, it highlights correlation outliers, which are potentially worth further examination. CONCLUSION: We anticipate PARE will facilitate comparative studies on mRNA and protein abundance by the proteomics community.

Helix Interaction Tool (HIT): a web-based tool for analysis of helix-helix interactions in proteins.

MOTIVATION: In many proteins, helix-helix interactions can be critical to establishing protein conformation (folding) and dynamics, as well as determining associations between protein units. However, the determination of a set of rules that guide helix-helix interaction has been elusive. In order to gain further insight into the helix-helix interface, we have developed a comprehensive package of tools for analyzing helix-helix packing in proteins. These tools are available at http://helix.gersteinlab.org. They include quantitative measures of the helix interaction surface area and helix crossing angle, as well as several methods for visualizing the helical interaction. These methods can be used for analysis of individual protein conformations or to gain insight into dynamic changes in helix interactions. For the latter purpose, a direct interface from entries in the Molecular Motions Database to the HIT site has been provided.