Self-assembly of a centriolar protein may contribute to organizing the cartwheel-like hub and establishing centriole symmetry.

The effect of lipids and nucleotides on the soluble head domain and membrane base domain is examined in an intact adenosine triphosphatase.

We present high resolution UV-photoelectron spectra of cold mass selected ${\mathrm{C}\mathrm{u}}_n^{-}$, ${\mathrm{A}\mathrm{g}}_n^{-}$, and ${\mathrm{A}\mathrm{u}}_n^{-}$ with $n=53–58$. The observed electron density of states is not the expected simple electron shell structure, but is strongly influenced by electron-lattice interactions. Only ${\mathrm{C}\mathrm{u}}_{55}^{-}$ and ${\mathrm{A}\mathrm{g}}_{55}^{-}$ exhibit highly degenerate states. This is a direct consequence of their icosahedral symmetry, as is confirmed by density functional theory calculations. Neighboring sizes exhibit perturbed electronic structures, as they are formed by removal or addition of atoms to the icosahedron and therefore have lower symmetries. Gold clusters in the same size range show completely different spectra with almost no degeneracy, which indicates that they have structures of much lower symmetry. This behavior is related to strong relativistic bonding effects in gold, as demonstrated by ab initio calculations for ${\mathrm{A}\mathrm{u}}_{55}^{-}$.

Multidrug resistance is a serious barrier to successful treatment of many human diseases, including cancer, wherein chemotherapeutics are exported from target cells by membrane-embedded pumps. The most prevalent of these pumps, the ATP-Binding Cassette transporter P-glycoprotein (P-gp), consists of two homologous halves each comprising one nucleotide-binding domain and six transmembrane helices. The transmembrane region encapsulates a hydrophobic cavity, accessed by portals in the membrane, that binds cytotoxic compounds as well as lipids and peptides. Here we use mass spectrometry (MS) to probe the intact P-gp small molecule-bound complex in a detergent micelle. Activation in the gas phase leads to formation of ions, largely devoid of detergent, yet retaining drug molecules as well as charged or zwitterionic lipids. Measuring the rates of lipid binding and calculating apparent K _D values shows that up to six negatively charged diacylglycerides bind more favorably than zwitterionic lipids. Similar experiments confirm binding of cardiolipins and show that prior binding of the immunosuppressant and antifungal antibiotic cyclosporin A enhances subsequent binding of cardiolipin. Ion mobility MS reveals that P-gp exists in an equilibrium between different states, readily interconverted by ligand binding. Overall these MS results show how concerted small molecule binding leads to synergistic effects on binding affinities and conformations of a multidrug efflux pump.