Cellular microbiology

Pathogenic bacteria attach to human fibronectin through a tandem β-zipper. Schwarz-Linek, U. et al. Nature 423, 177–181 (2003)

These authors used a structural approach to understand bacterial fibronectin-binding protein (FnBP)-mediated adhesion to host cells. They determined the structure of a streptococcal FnBP peptide (B3) in complex with modules 1 and 2 (1F12F1) of the amino-terminal, bacterium-binding site of host-cell fibronectin. The interaction seen is the first example of a tandem β-zipper, in which β-strands form on adjacent domains (in this case, the sequential F1 modules).

Molecular motors

Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Hafezparast, M. et al. Science 300, 808–812 (2003)

The underlying genetic defects of many motor neuron diseases, including most amyotrophic lateral sclerosis (ALS) cases, are unknown. But, Hafezparast et al. now show that missense point mutations in the cytoplasmic dynein heavy chain 1 (Dnchc1) gene cause progressive motor neuron degeneration in heterozygous mice, and that homozygous mice present with Lewy-like inclusion bodies. Dnchc1 mutations are thought to impair fast retrograde transport in spinal-cord motor neurons.

Signal transduction

Switch-of-function mutants based on morphology classification of Ras superfamily small GTPases. Do Heo, W. & Meyer, T. Cell 113, 315–328 (2003)

Proteins from the same family can have very different functional roles. Indeed, these authors found that cell morphology changes induced by constitutively active small GTPases could be grouped into nine classes. To find out which amino acids in a functional class are relevant for functional specificity, they developed a 'switch-of-class' algorithm, which was validated experimentally. Surprisingly, residues that define morphology were mostly outside the known interaction surfaces and were structurally far apart from each other.

Cell adhesion

Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow. Shimonaka, M. et al. J. Cell Biol. 161, 417–427 (2003)

Lymphocytes migrate in response to chemokines in a process that requires adhesive interactions with the vascular endothelium. Shimonaka et al. now show that the small GTPase Rap1 is crucially involved in the chemokine-mediated rapid increase of the adhesive activity of two integrins to immobilized intercellular adhesion molecule-1 (ICAM-1). Rap1 also causes increased cell migration and cell polarization in lymphocytes.