Microtubules are filamentous polymers essential for cell viability. Microtubule plus-end tracking proteins (+TIPs) associate with growing microtubule plus ends and control microtubule dynamics and interactions with different cellular structures during cell division, migration, and morphogenesis. EB1 and its homologs are highly conserved proteins that play an important role in the targeting of +TIPs to microtubule ends, but the underlying molecular mechanism remains elusive. By using live cell experiments and in vitro reconstitution assays, we demonstrate that a short polypeptide motif, Ser-x-Ile-Pro (SxIP), is used by numerous +TIPs, including the tumor suppressor APC, the transmembrane protein STIM1, and the kinesin MCAK, for localization to microtubule tips in an EB1-dependent manner. Structural and biochemical data reveal the molecular basis of the EB1-SxIP interaction and explain its negative regulation by phosphorylation. Our findings establish a general "microtubule tip localization signal" (MtLS) and delineate a unifying mechanism for this subcellular protein targeting process.

In all eukaryotes, CAP-Gly proteins control important cellular processes. The molecular mechanisms underlying the functions of CAP-Gly domains, however, are still poorly understood. Here we use the complex formed between the CAP-Gly domain of p150(glued) and the C-terminal zinc knuckle of CLIP170 as a model system to explore the structure-function relationship of CAP-Gly-mediated protein interactions. We demonstrate that the conserved GKNDG motif of CAP-Gly domains is responsible for targeting to the C-terminal EEY/F sequence motifs of CLIP170, EB proteins and microtubules. The CAP-Gly-EEY/F interaction is essential for the recruitment of the dynactin complex by CLIP170 and for activation of CLIP170. Our findings define the molecular basis of CAP-Gly domain function, including the tubulin detyrosination-tyrosination cycle. They further establish fundamental roles for the interaction between CAP-Gly proteins and C-terminal EEY/F sequence motifs in regulating complex and dynamic cellular processes.

The syntheses of the new compounds Fe(3-Me 3 Si-6,6-dmch) 2 , 2, and Fe[3-(i-Pr) 3 Si-6,6-dmch] 2 , 3, are reported, along with X-ray structural studies of these species, and of the previously reported Fe(1,3,5,6-temch) 2 (dmch ) dimethylcyclohexadienyl; temch ) tetramethylcyclohexadienyl). Each species crystallized in something close to the expected gauche-eclipsed conformation. In accord with previous work on Fe(6,6-dmch) 2 , but in contrast to results for open ferrocenes such as Fe(2,4-C 7 H 11 ) 2 (C 7 H 11 ) dimethylpentadienyl), the three species under study undergo reversible one-electron oxidations at room temperature to stable 17-electron cations, with potentials for oxidation being more favorable than that for ferrocene by 0.51-0.78 V. The edge-bridged open ferrocenes also react in a 1:1 ratio with TCNE (TCNE ) tetracyanoethylene), yielding salts that were shown spectroscopically to contain the expected cationic 17-electron metal complexes and the TCNE radical anion.

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