A Comparison of Carbon-Carbon Double Bond and Cyclopropane as Neighboring Groups. Solvolysis Rates of 1-Aryl-4-cyclopropylbutyl Chlorides

1-Phenyl-4-cyclopropylbutyl chloride 13a and 1-m-bromophenyl- 4-cyclopropylbutyl chloride 13b were prepared and their solvolysis rates measured. As with corresponding 1-aryl-5-hexenyl chlorides 9, no reaction rate increases were observed. In contrast, 1-aryl-5-methyl-5-hexenyl chlorides 10 and 1-aryl-5-heptenyl chlorides 11 which are isomeric to 13 solvolyze with significant anchimeric assistance of the methyl-substituted aliphatic double bond. This failure of the cyclopropane ring to act as a neighboring group is rationalized in terms of possible charge delocalization in the reaction transition state arising from 13 and from 10 or 11

SLAIN2 links microtubule plus end–tracking proteins and controls microtubule growth in interphase

SLAIN2’s interactions with multiple different microtubule plus end–tracking proteins stimulate processive microtubule polymerization and ensure proper microtubule organization

Classification and function of small open reading frames

Small open reading frames (smORFs) of 100 codons or fewer are usually - if arbitrarily - excluded from proteome annotations. Despite this, the genomes of many metazoans, including humans, contain millions of smORFs, some of which fulfil key physiological functions. Recently, the transcriptome of Drosophila melanogaster was shown to contain thousands of smORFs of different classes that actively undergo translation, which produces peptides of mostly unknown function. Here, we present a comprehensive analysis of smORFs in flies, mice and humans. We propose the existence of several functional classes of smORFs, ranging from inert DNA sequences to transcribed and translated cis-regulators of translation and peptides with a propensity to function as regulators of membrane-associated proteins, or as components of ancient protein complexes in the cytoplasm. We suggest that the different smORF classes could represent steps in gene, peptide and protein evolution. Our analysis introduces a distinction between different peptide-coding classes of smORFs in animal genomes, and highlights the role of model organisms for the study of small peptide biology in the context of development, physiology and human disease

A comparison of carbon-carbon double bond and cyclopropane as neighboring groups. Solvolysis rates of 1-aryl-4-cyclopropylbutyl chlorides

1-Phenyl-4-cyclopropylbutyl chloride 13a and 1-m-bromophenyl- 4-cyclopropylbutyl chloride 13b were prepared and their solvolysis rates measured. As with corresponding 1-aryl-5-hexenyl chlorides 9, no reaction rate increases were observed. In contrast, 1-aryl-5-methyl-5-hexenyl chlorides 10 and 1-aryl-5-heptenyl chlorides 11 which are isomeric to 13 solvolyze with significant anchimeric assistance of the methyl-substituted aliphatic double bond. This failure of the cyclopropane ring to act as a neighboring group is rationalized in terms of possible charge delocalization in the reaction transition state arising from 13 and from 10 or 11

Molecular Insights into Mammalian End-binding Protein Heterodimerization*

Microtubule plus-end tracking proteins (+TIPs) are involved in many microtubule-based processes. End binding (EB) proteins constitute a highly conserved family of +TIPs. They play a pivotal role in regulating microtubule dynamics and in the recruitment of diverse +TIPs to growing microtubule plus ends. Here we used a combination of methods to investigate the dimerization properties of the three human EB proteins EB1, EB2, and EB3. Based on Förster resonance energy transfer, we demonstrate that the C-terminal dimerization domains of EBs (EBc) can readily exchange their chains in solution. We further document that EB1c and EB3c preferentially form heterodimers, whereas EB2c does not participate significantly in the formation of heterotypic complexes. Measurements of the reaction thermodynamics and kinetics, homology modeling, and mutagenesis provide details of the molecular determinants of homo- versus heterodimer formation of EBc domains. Fluorescence spectroscopy and nuclear magnetic resonance studies in the presence of the cytoskeleton-associated protein-glycine-rich domains of either CLIP-170 or p150glued or of a fragment derived from the adenomatous polyposis coli tumor suppressor protein show that chain exchange of EBc domains can be controlled by binding partners. Extension of these studies of the EBc domains to full-length EBs demonstrate that heterodimer formation between EB1 and EB3, but not between EB2 and the other two EBs, occurs both in vitro and in cells as revealed by live cell imaging. Together, our data provide molecular insights for rationalizing the dominant negative control by C-terminal EB domains and form a basis for understanding the functional role of heterotypic chain exchange by EBs in cells