Morgane Boone

This study identifies an allosteric mechanism in eIF2B that regulates the Integrated Stress Response by showing how eIF2-P binding inhibits eIF2B activity through latch-helix dislocation.

The paper demonstrates that a modified ISRIB analog selectively targets a mutant eIF2B, improving synaptic plasticity and memory in mice, confirming its on-target mechanism.

The paper shows how a point mutation in eIF2B's β subunit mimics eIF2-P binding, leading to constitutive activation of the integrated stress response through an I-State conformation.

The paper develops SECRiFY, a method to assess secretability of protein fragments in yeast, revealing intrinsic disorder and flexibility as key factors.

Inhibition of the integrated stress response restores neuronal and immune dysfunction and alleviates memory deficits in aged mice.