Mitochondrial Bol1 and Bol3 function as assembly factors for specific iron-sulfur proteins

Assembly of mitochondrial iron-sulfur (Fe/S) proteins is a key process of cells, and defects cause many rare diseases. In the first phase of this pathway, ten Fe/S cluster (ISC) assembly components synthesize and insert [2Fe-2S] clusters. The second phase is dedicated to the assembly of [4Fe-4S] proteins, yet this part is poorly understood. Here, we characterize the BOLA family proteins Bol1 and Bol3 as specific mitochondrial ISC assembly factors that facilitate [4Fe-4S] cluster insertion into a subset of mitochondrial proteins such as lipoate synthase and succinate dehydrogenase. Bol1-Bol3 perform largely overlapping functions, yet cannot replace the ISC protein Nfu1 that also participates in this phase of Fe/S protein biogenesis. Bol1 and Bol3 form dimeric complexes with both monothiol glutaredoxin Grx5 and Nfu1. Complex formation differentially influences the stability of the Grx5-Bol-shared Fe/S clusters. Our findings provide the biochemical basis for explaining the pathological phenotypes of patients with mutations in BOLA3. DOI: http://dx.doi.org/10.7554/eLife.16673.00

Anticipatory anti-colonial writing in R.K. Narayan's Swami and Friends and Mulk Raj Anand's Untouchable

This article uses the term “anticipatory anti-colonial writing” to discuss the workings of time in R.K. Narayan’s Swami and Friends and Mulk Raj Anand’s Untouchable. Both these first novels were published in 1935 with the support of British literary personalities (Graham Greene and E.M. Forster respectively) and both feature young protagonists who, in contrasting ways, are engaged in Indian resistance to colonial rule. This study examines the difference between Narayan’s local, though ironical, resistance to the homogenizing temporal demands of empire and Anand’s awkwardly modernist, socially committed vision. I argue that a form of anticipation that explicitly looks forward to decolonization via new and transnational literary forms is a crucial feature of Untouchable that is not found in Swami and Friends, despite the latter’s anti-colonial elements. Untouchable was intended to be a “bridge between the Ganges and the Thames” and anticipates postcolonial negotiations of time that critique global inequalities and rely upon the multidirectional global connections forged by modernism

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A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation.

Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines