News Center

Berkeley Lab and Scripps Research Institute Scientists Link ALS Progression to Increased Protein Instability


LA JOLLA, CA—October 13, 2014—A new study by scientists from The Scripps Research Institute (TSRI), Lawrence Berkeley National Laboratory (Berkeley Lab) and other institutions suggests a cause of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. “Our work supports a common theme whereby loss of protein stability leads to disease,” said John A.

Bright Future for Protein Nanoprobes

Berkeley Lab researchers at the Molecular Foundry have discovered surprising new rules for creating ultra-bright light-emitting crystals that are less than 10 nanometers in diameter. These ultra-tiny but ultra-bright nanoprobes should be a big asset for biological imaging, especially deep-tissue optical imaging of neurons in the brain.

Bringing Out the Best in X-ray Crystallography Data

Combining components of Rosetta and PHENIX, two successful software programs for creating 3D structural models of proteins and other biomolecules, Berkeley Lab researchers have created a new method for refining those models and making the best of available experimental data.

Comparing Proteins at a Glance

A revolutionary X-ray analytical technique enables researchers at a glance to identify structural similarities and differences between multiple proteins under a variety of conditions and has already been used to gain valuable new insight into a prime protein target for cancer chemotherapy.

Revealing the Secrets of Motility in Archaea


The protein structure of the archaellum, the motor that propels many species of Archaea, the third domain of life, has been characterized for the first time by a team from Berkeley Lab and the Max Planck Institute for Terrestrial Microbiology. A ring made of six identical proteins derives energy from hydrolyzing adenosine triphosate (ATP) and uses this energy to drive shape changes, both assembling and rotating the archaellum’s whiplike propeller.

Correct Protein Folding:

Berkeley Lab researchers at the Advanced Light Source have discovered a nucleotide-sensing loop that synchronizes conformational changes in the three domains of group II chaperonin for the proper folding of other proteins.

Using the exceptionally bright and powerful x-ray beams of the Advanced Light Source, Berkeley Lab researchers have discovered a critical control element within chaperonin, the protein complex responsible for the correct folding of other proteins. The “misfolding” of proteins has been linked to many diseases, including Alzheimer’s, Parkinson’s and some forms of cancer.

How Key Genes Cooperate to Make Healthy Skin

At top, p63 proteins labeled pink and Satb1 proteins labeled green are expressed together in the nuclei of cells in a normal (wild-type) developing epidermis. At bottom, green-glowing Satb1 is abundant in the epidermis of a wild-type mouse, but in a mouse without the p63 gene, Satb1 is not expressed.

An essential relationship among leading genes and proteins that control the health of the skin has been revealed by a multinational research team. The protein p63 is the “master regulator” for skin’s uppermost layers, the epidermis. It does much of its work by directly controlling the chromatin-remodeling protein Satb1, discovered at Berkeley Lab over a decade ago and already known for critical roles in the immune system and aggressive breast cancer.

Safeguarding Genome Integrity Through Extraordinary DNA Repair

Heterochromatin (purple) accounts for a third of the chromatin in both humans and fruit flies. Some heterochromatin forms the telomeres that cap the ends of the chromatids, and much is concentrated near the centromere, where sister chromatids are joined. Accurate repair of double-strand breaks in heterochromatin is challenging, because most of its DNA consists of short, repeated sequences.

Once called “junk DNA” because it contains numerous repeated short sequences that don’t code for proteins, heterochromatin is in fact vital for normal growth and function. Yet it poses special challenges to accurate DNA repair. Berkeley Lab life scientists have discovered an unsuspected and dramatic process by which double-strand breaks in heterochromatin are repaired in dynamic stages.

Secrets of a Precision Protein Machine

During DNA replication of the lagging strand, numerous Okazaki fragments must be joined. The newer fragment ends in a short flap call the 3’ overhang, while the previous fragment leaves a long 5’ flap after its primer is removed. The junction opens when the template strand is bent 100 degrees. FEN1 grasps the DNA at the bend, threads the flap through an archway, and trims the flap to match the overhang. (Click on image for best resolution.)

The structure of the DNA-slicing protein FEN1, an essential player in human DNA replication, has been solved by an international team of life scientists led by researchers at Berkeley Lab and the Scripps Research Institute. FEN1 cuts the “flaps” leftover when new fragments of DNA are assembled during replication and also plays a role in DNA repair. Its protein structure reveals the surprising mechanism behind FEN1’s speed, accuracy, and versatility.