SAR by NMR: putting the pieces together

It has been nearly ten years since the introduction of SAR by NMR and the advent of fragment-based drug design. During this time, we have gained a tremendous amount of knowledge about protein druggability, the limits of chemical diversity, and crafting high-affinity ligands from low molecular weight, weakly binding leads. This review will describe the concept of fragment-based drug design, discuss why it works, and illustrate the power of the approach with two case studies on the design of potent inhibitors of matrix metalloproteinases and Bcl-2 family proteins.     

UniCarbKB: putting the pieces together for glycomics research

Despite the success of several international initiatives the glycosciences still lack a managed infrastructure that contributes to the advancement of research through the provision of comprehensive structural and experimental glycan data collections. UniCarbKB is an initiative that aims to promote the creation of an online information storage and search platform for glycomics and glycobiology research. The knowledgebase will offer a freely accessible and information-rich resource supported by querying interfaces, annotation technologies and the adoption of common standards to integrate structural, experimental and functional data. The UniCarbKB framework endeavors to support the growth of glycobioinformatics and the dissemination of knowledge through the provision of an open and unified portal to encourage the sharing of data. In order to achieve this, the framework is committed to the development of tools and procedures that support data annotation, and expanding interoperability through cross-referencing of existing databases. Database URL: http://www.unicarbkb.org.     

Rheumatoid arthritis and smoking: putting the pieces together

Besides atherosclerosis and lung cancer, smoking is considered to play a major role in the pathogenesis of autoimmune diseases. It has long been known that there is a connection between rheumatoid factor-positive rheumatoid arthritis and cigarette smoking. Recently, an important gene–environment interaction has been revealed; that is, carrying specific HLA-DRB1 alleles encoding the shared epitope and smoking establish a significant risk for anti-citrullinated protein antibody-positive rheumatoid arthritis. We summarize how smoking-related alteration of the cytokine balance, the increased risk of infections (the possibility of cross-reactivity) and modifications of autoantigens by citrullination may contribute to the development of rheumatoid arthritis.     

Amino acid determinants of alpha-synuclein aggregation: putting together pieces of the puzzle

The centrosome is the major microtubule-organizing center of animal cells. It influences cell shape and polarity and directs the formation of the bipolar mitotic spindle. Numerical and structural centrosome aberrations have been implicated in disease, notably cancer. In dividing cells, centrosomes need to be duplicated and segregated in synchrony with chromosomes. This centrosome cycle requires a series of structural and functional transitions that are regulated by both phosphorylation and proteolysis. Here we summarize recent information on the regulation of the centrosome cycle and its coordination with the chromosomal cell cycle.     

Clathrin-associated adaptor proteins - putting it all together

Adaptors are multifunctional linker proteins that, as a coated vesicle assembles, tether the clathrin lattice to the underlying membrane bud site. Each adaptor is composed of four distinct protein submits, but how these assemble into the functional complex is not clear. Here, some features of the protein sequences are discussed in an attempt to develop a speculative, low-resolution structural model of possible subunit interactions.     

The multifaceted relationship between IL-10 and adaptive immunity: putting together the pieces of a puzzle

Interleukin-10 (IL-10) is a pleiotropic cytokine that modulates the function of several adaptive immunity-related cells. Although generally considered an immunosuppressive molecule, IL-10 possesses immunostimulatory properties in several in vitro and in vivo models. These very different outcomes are believed to depend upon experimental conditions, the dominant immune effector mediating a given immune response, the timing of IL-10 production/administration, and IL-10 dose and/or location of expression. In the present work, we review the current knowledge regarding IL-10 activity on adaptive immunity related cells, emphasize new insights on IL-10 molecular/cellular targets, and summarize the available data on the relationship between IL-10 and some pathological conditions (e.g. infectious diseases, autoimmunity, allergy, cancer and transplantation) involving adaptive immunity.     

Color vision: putting it together

Color vision depends on the visual system comparing signals that originate in different classes of cone photoreceptors. New work shows that the different classes of cones are not only distributed irregularly, but in different individuals they are present in very variable proportions. Surprisingly, this does not affect color vision.     

Primary cilia: putting sensors together

Primary cilia extend like antennae from the surface of most eukaryotic cells into the environment, where they function in a variety of sensory roles. Recent studies reveal an intimate interplay between structural proteins of the centrosome and the formation of primary cilia, and provide new insight into the complex function of these fascinating organelles.