The Crystal Structure of Monovalent Streptavidin.

The strong interaction between streptavidin (SA) and biotin is widely utilized in biotechnological applications. A SA variant, monovalent SA, was developed with a single and high affinity biotin-binding site within the intact tetramer. However, its structural characterization remains undetermined. Here, we seek to determine the crystal structure of monovalent SA at 1.7-Å resolution. We show that, in contrast to its 'close-state' in the only wild-type subunit, the L3,4 loops of three Dead SA subunits are free from crystal packing and remain in an 'open state', stabilized by a consistent H-bonding network involving S52. This H-bonding network also applies to the previously reported open state of the wild-type apo-SA. These results suggest that specific substitutions (N23A/S27D/S45A) at biotin-binding sites stabilize the open state of SA L3,4 loop, thereby further reducing biotin-binding affinity. The general features of the 'open state' SA among different SA variants may facilitate its rational design. The structural information of monovalent SA will be valuable for its applications across a wide range of biotechnological areas

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

The role of Notch pathway in tumorigenesis is highly variable. It can be tumor suppressive or pro-oncogenic, typically depending on the cellular context. Squamous cell carcinoma (SCC) is a cancer of the squamous cell, which can occur in diverse human tissues. SCCs are one of the most frequent human malignancies for which the pathologic mechanisms remain elusive. Recent genomic analysis of diverse SCCs identified marked levels of mutations in NOTCH1, implicating Notch signaling pathways in the pathogenesis of SCCs. In this review, evidences highlighting NOTCH's role in different types of SCCs are summarized. Moreover, based on accumulating structural information of the NOTCH receptor, the functional consequences of NOTCH1 gene mutations identified from diverse SCCs are analyzed, emphasizing loss of function of Notch in these cancers. Finally, we discuss the convergent view on an intriguing possibility that Notch may function as tumor suppressor in SCCs across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCCs and development of therapeutic strategies for these cancers

Further improvements on a global nuclear mass model

The semi-empirical macroscopic-microscopic mass formula is further improved by considering some residual corrections. The rms deviation from 2149 known nuclear masses is significantly reduced to 336 keV, even lower than that achieved with the best of the Duflo-Zuker models. The alpha-decay energies of super-heavy nuclei, the Garvey-Kelson relations and the isobaric multiplet mass equation (IMME) can be reproduced remarkably well with the model, and the predictive power of the mass model is good. With a systematic study of 17 global nuclear mass models, we find that the quadratic form of the IMME is closely related to the accuracy of nuclear mass calculations when the Garvey-Kelson relations are reproduced reasonably well. Fulfilling both the IMME and the Garvey-Kelson relations seems to be two necessary conditions to improve the quality of the model prediction. Furthermore, the alpha-decay energies of super-heavy nuclei should be used as an additional constraint on the global nuclear mass models.Comment: 10 figures, 2 tables; version to appear in Phys. Rev.