Mass Spec Roundup: Antigens, Hooks, and Heat… 

Peptide Mapping Reveals Key TB Vaccine Antigens 

In the search for a more effective tuberculosis (TB) vaccine, MIT researchers have mapped how human immune cells display fragments of Mycobacterium tuberculosis (Mtb) proteins – revealing new targets for vaccine design. The study, published in Science Translational Medicine, identifies a set of immunogenic peptides that trigger robust helper T-cell responses, potentially paving the way for the first major TB vaccine advance in a century. 

Analyzing more than 4,000 Mtb proteins, the team found 24 peptides that consistently activated T cells from people previously infected with TB. Many came from type VII secretion system (T7SS) proteins such as EsxA, EsxB, and EsxG – molecules that help the bacterium evade host defenses. Using mRNA constructs encoding combinations of these proteins, the researchers achieved up to 1,000-fold higher peptide presentation when targeted to lysosomes, boosting immune recognition. 

“There’s still a huge TB burden globally that we’d like to make an impact on,” said Bryan Bryson, associate professor of biological engineering at MIT and member of the Ragon Institute. “What we’ve tried to do is focus on antigens that we saw frequently in our screen and that also appear to stimulate a response in T cells from people with prior TB infection.” 

Hooked on a Protein 

For the first time, scientists have mapped the structural “hook” that lets neurons identify and transport their molecular cargo with pinpoint accuracy. The study, published in Science Advances, reveals how the motor protein kinesin-2 uses a newly discovered hook-like adaptor and cargo-binding (HAC) domain to connect with its cargo protein, adenomatous polyposis coli (APC). 

Using cryo-electron microscopy, molecular dynamics simulations, and cross-linking mass spectrometry, the team led by Nobutaka Hirokawa at Juntendo University reconstructed the KIF3A/KIF3B/KAP3–APC complex at near-atomic resolution. They found that the HAC domain, a helix–β-hairpin–helix motif in the kinesin-2 tail, forms a scaffold for adaptor protein KAP3 and the ARM repeat region of APC, establishing four distinct binding interfaces.  

“Our study has uncovered a previously unknown ‘hook-like’ structural element, the HAC domain, in the tail of the motor protein kinesin-2,” said Hirokawa in the team’s press release. “This domain acts as a molecular ‘connector’ that allows the motor to correctly recognize and transport its cargo inside cells.” 

The researchers propose that the HAC/KAP3 architecture echoes cargo-recognition modules in dynein and kinesin-1, hinting at a shared evolutionary logic for intracellular logistics. “Our new findings provide the first atomic-level insight into this ‘logistics code’ of cellular transport,” Hirokawa added – laying the molecular groundwork for understanding neurodegenerative diseases linked to transport failure. 

Temperature Controls Catalyst Pathway in Water-Splitting Reaction 

Researchers at Tohoku University have revealed that temperature can flip the reaction mechanism of a promising oxygen evolution catalyst, potentially redefining how scientists design materials for efficient water splitting. The study, published in Nature Communications, shows that RhRu₃Oₓ follows distinct catalytic routes at different temperatures, shedding light on how thermal effects shape electrochemical performance. 

Using a custom-built operando differential electrochemical mass spectrometry (DEMS) setup, the team tracked oxygen evolution in real time under acidic conditions. The analyses showed that RhRu₃Oₓ transitions from one oxygen evolution reaction (OER) mechanism to another as temperature rises – an effect confirmed by Arrhenius plots and electrochemical impedance spectroscopy (EIS). “We found that this catalyst tends towards different reaction mechanisms at high versus low temperatures, which we can now use to our advantage,” said Heng Liu of the Advanced Institute for Materials Research (AIMR). 

The catalyst also demonstrated exceptional durability, remaining active for over 1,000 hours at room temperature under a current density of 200 mA cm⁻². The authors suggest that tuning temperature-dependent kinetics – and optimizing fluorine doping – could improve both efficiency and stability in proton-exchange membrane (PEM) electrolyzers. 

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