The Protein Coil Library: a structural database of nonhelix, nonstrand fragments derived from the PDB

Approximately half the structure of folded proteins is either alpha-helix or beta-strand. We have developed a convenient repository of all remaining structure after these two regular secondary structure elements are removed. The Protein Coil Library (http://roselab.jhu.edu/coil/) allows rapid and comprehensive access to non-alpha-helix and non-beta-strand fragments contained in the Protein Data Bank (PDB). The library contains both sequence and structure information together with calculated torsion angles for both the backbone and side chains. Several search options are implemented, including a query function that uses output from popular PDB-culling servers directly. Additionally, several popular searches are stored and updated for immediate access. The library is a useful tool for exploring conformational propensities, turn motifs, and a recent model of the unfolded state.     

Steric restrictions in protein folding: an alpha-helix cannot be followed by a contiguous beta-strand

Using only hard-sphere repulsion, we investigated short polyalanyl chains for the presence of sterically imposed conformational constraints beyond the dipeptide level. We found that a central residue in a helical peptide cannot adopt dihedral angles from strand regions without encountering a steric collision. Consequently, an alpha-helical segment followed by a beta-strand segment must be connected by an intervening linker. This restriction was validated both by simulations and by seeking violations within proteins of known structure. In fact, no violations were found within an extensive database of high-resolution X-ray structures. Nature's exclusion of alpha-beta hybrid segments, fashioned from an alpha-helix adjoined to a beta-strand, is built into proteins at the covalent level. This straightforward conformational constraint has far-reaching consequences in organizing unfolded proteins and limiting the number of possible protein domains.     

Plagiarism of the host immune system: lessons about chemokine immunology from viruses

In their attempts to evade the host immune response, mammalian viruses have evolved a wide range of strategies. These include the expression and modification of various host cytokines and receptors. Understanding the mechanism of action of these virally encoded proteins will clearly deepen our insights into immunology. In the past few months several new virally encoded chemokines have been described which can modify both the host immune and antiviral response. Their manipulation of the cytokine structure-function relationship may also be useful in the development of reagents for treating immune and proliferative diseases.