Structural insight into the SAM-mediated assembly of the mitochondrial TOM core complex.

β barrel outer membrane proteins (β-OMPs) play vital roles in mitochondria, chloroplasts, and Gram-negative bacteria. Evolutionarily conserved complexes such as the mitochondrial sorting and assembly machinery (SAM) mediate the assembly of β-OMPs. We investigated the SAM-mediated assembly of the translocase of the outer membrane (TOM) core complex.

Cataract-causing mutation S228P promotes βB1-crystallin aggregation and degradation by separating two interacting loops in C-terminal domain.

β/γ-Crystallins are predominant structural proteins in the cytoplasm of lens fiber cells and share a similar fold composing of four Greek-key motifs divided into two domains. Numerous cataract-causing mutations have been identified in various β/γ-crystallins, but the mechanisms underlying cataract caused by most mutations remains uncharacterized. The S228P mutation in βB1-crystallin has been linked to autosomal dominant congenital nuclear cataract.

Congenital microcornea-cataract syndrome-causing mutation X253R increases βB1-crystallin hydrophobicity to promote aggregate formation.

The high solubility and lifelong stability of crystallins are crucial to the maintenance of lens transparency and optical properties. Numerous crystallin mutations have been linked to congenital cataract, which is one of the leading causes of newborn blindness. Besides cataract, several crystallin mutations have also been linked to syndromes such as congenital microcornea-cataract syndrome (CMCC).

The N-terminal extension of βB1-crystallin chaperones β-crystallin folding and cooperates with αA-crystallin.

β/γ-Crystallins are the major structural proteins in mammalian lens. The N-terminal truncation of βB1-crystallin has been associated with the regulation of β-crystallin size distributions in human lens. Herein we studied the roles of βB1 N-terminal extension in protein structure and folding by constructing five N-terminal truncated forms.