Two WXXF-based motifs in NECAPs define the specificity of accessory protein binding to AP-1 and AP-2

The adaptor proteins AP-2 and AP-1/GGAs are essential components of clathrin coats at the plasma membrane and trans-Golgi network, respectively. The adaptors recruit accessory proteins to clathrin-coated pits, which is dependent on the adaptor ear domains engaging short peptide motifs in the accessory proteins. Here, we perform an extensive mutational analysis of a novel WXXF-based motif that functions to mediate the binding of an array of accessory proteins to the alpha-adaptin ear domain of AP-2. Using nuclear magnetic resonance and mutational studies, we identified WXXF-based motifs as major ligands for a site on the alpha-ear previously shown to bind the DPW-bearing proteins epsin 1/2. We also defined the determinants that allow for specific binding of the alpha-ear motif to AP-2 as compared to those that allow a highly related WXXF-based motif to bind to the ear domains of AP-1/GGAs. Intriguingly, placement of acidic residues around the WXXF cores is critical for binding specificity. These studies provide a structural basis for the specific recruitment of accessory proteins to appropriate sites of clathrin-coated vesicle formation.     

Three new compounds from the plant Lippia alva as inhibitors of chemokine receptor 5 (CCR5)

The 70% aqueous methanol extract of the Peruvian plant Lippia alva (Verbenaceae) was found to contain three novel compounds, 1, 2, and 3, which were identified as inhibitors of the chemokine receptor CCR5. The structures of 1-3 were established based on extensive NMR studies. Compounds 1-3 inhibited CCR5 receptor signaling as measured by a calcium mobilization assay with IC(50) values of 5.5, 6.0, and 7.2 microg/mL, respectively.     

Structural proteomics: a tool for genome annotation

In any newly sequenced genome, 30% to 50% of genes encode proteins with unknown molecular or cellular function. Fortunately, structural genomics is emerging as a powerful approach of functional annotation. Because of recent developments in high-throughput technologies, ongoing structural genomics projects are generating new structures at an unprecedented rate. In the past year, structural studies have identified many new structural motifs involved in enzymatic catalysis or in binding ligands or other macromolecules (DNA, RNA, protein). The efficiency by which function is deduced from structure can be further improved by the integration of structure with bioinformatics and other experimental approaches, such as screening for enzymatic activity or ligand binding.     

Diverse roles of eph receptors and ephrins in the regulation of cell migration and tissue assembly

Eph receptor tyrosine kinases and ephrins have key roles in regulation of the migration and adhesion of cells required to form and stabilize patterns of cell organization during development. Activation of Eph receptors or ephrins can lead either to cell repulsion or to cell adhesion and invasion, and recent work has found that cells can switch between these distinct responses. This review will discuss biochemical mechanisms and developmental roles of the diverse cell responses controlled by Eph receptors and ephrins.     

Ancient DNA: would the real Neandertal please stand up?

Mitochondrial DNA sequences recovered from eight Neandertal specimens cannot be detected in either early fossil Europeans or in modern populations. This indicates that, if Neandertals made any genetic contribution at all to modern humans, it must have been limited, though the extent of the contribution cannot be resolved at present.     

A transporter of<Emphasis Type="Italic"> Escherichia coli</Emphasis> specific for<Emphasis Type="SmallCaps"> l</Emphasis>- and<Emphasis Type="SmallCaps"> d</Emphasis>-methionine is the prototype for a new family within the ABC superfamily

An ABC-type transporter in Escherichia coli that transports both l- and d-methionine, but not other natural amino acids, was identified. This system is the first functionally characterized member of a novel family of bacterial permeases within the ABC superfamily. This family was designated the methionine uptake transporter (MUT) family (TC #3.A.1.23). The proteins that comprise the transporters of this family were analyzed phylogenetically, revealing the probable existence of several sequence-divergent primordial paralogues, no more than two of which have been transmitted to any currently sequenced organism. In addition, MetJ, the pleiotropic methionine repressor protein, was shown to negatively control expression of the operon encoding the ABC-type methionine uptake system. The identification of MetJ binding sites (in gram-negative bacteria) or S-boxes (in gram-positive bacteria) in the promoter regions of several MUT transporter-encoding operons suggests that many MUT family members transport organic sulfur compounds. Electronic Supplementary Material Supplementary material is available for this article if you access the article at . A link in the frame on the left on that page takes you directly to the supplementary material.