Using the computer game, “Foldit,” nonexpert citizen scientists designed new proteins whose structures, verified at the ALS, were equivalent in quality to and more structurally diverse than computer-generated designs. The work shows the potential of using crowd-based creativity in the design of new proteins for fighting illness and disease. Read more »
X-Ray Studies Key in Study Relating to Immune System-Signaling Protein
A grouping of amino acids—part of an important signaling protein, STING—plays an important role in activating the immune system. A study conducted through the Collaborative Crystallography program at the ALS confirmed how this part of the STING protein helps to bind a protein-modifying enzyme associated with autoimmune diseases and some cancers. Read more »
Self-Assembling 2D Arrays with de Novo Protein Building Blocks
Modular self-assembly of biomolecules in two dimensions (2D) is straightforward with DNA but has been difficult to realize with proteins, due to the lack of modular specificity similar to Watson–Crick base pairing. Here, researchers describe a general approach to designing 2D arrays using de novo designed pseudosymmetric protein building blocks. Read more »
Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders
PDE4D enzymes are important for normal brain function. Mutations have been asssociated with an ultrarare neurodevelopmental disorder, and genetic variation in PDE4D contributes to biological variation in human cognitive ability. Here, researchers report on novel PDE4D inhibitors providing potent memory-enhancing effects in a mouse model, with improved tolerability and reduced vascular toxicity over earlier PDE4 inhibitors. Read more »
Structural Characterization of a Synthetic Tandem-Domain Bacterial Microcompartment Shell Protein Capable of Forming Icosahedral Shell Assemblies
Bacterial microcompartments (BMCs) are subcellular compartments found in many prokaryotes, and they are of considerable interest for biotechnological applications. The BMC-H2 shell system constitutes a relatively simple generic building block that could be used to construct designed shells with a relatively highly tunable pore. Read more »
Locking Protein Structure to Close the Door on Cancer
While the SHP2 protein helps regulate cellular activity, mutations in its structure can lead to cancer. X-ray crystallography at the ALS and SSRL has revealed differences between normal and mutated SHP2, as well as how it binds to certain cancer drugs. These structural insights open the door to new types of cancer therapy. Read more »
Structure Reveals Mechanism Behind Periodic Paralysis
X-ray crystallography of a membrane protein provided a structural understanding of how a single mutation can result in periodic muscle paralysis. The results suggest possible drug designs that could provide relief to patients with a genetic disorder that causes them to be overcome suddenly with profound muscle weakness. Read more »
Open and Shut: Pain Signals in Nerve Cells
Researchers used x-ray data to define the structure of a closed protein gate important for neuronal signaling. Comparing the closed gate with previously known structures of the same gate when open, researchers now have a comprehensive picture of proton-dependent channels in neurons. Read more »
Structures Reveal New Target for Malaria Vaccine
Researchers isolated human-derived antibodies that protect against malaria, and protein-structure studies revealed the antibodies’ site of attack. The discovery paves the way for the development of a more effective and practical human vaccine for malaria, which is responsible for half a million deaths every year. Read more »
ALS Passes the 7000-Protein Milestone
The eight structural biology beamlines at the ALS have now collectively deposited over 7000 proteins into the Protein Data Bank (PDB), a worldwide, open-access repository of protein structures. The 7000th ALS protein (entry no. 6C7C) is an enzyme from Mycobacterium ulcerans (strain Agy99), solved with data from Beamline 5.0.2. Read more »
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