Ewelina Guca

Translation initiation in eukaryotes is a complex multistep process that requires the interplay of over a dozen protein factors together with the small ribosomal subunit (SSU) and the mRNA. During all these steps, the SSU serves as a platform for attachment, displacement and release of different molecules. In recent years, the great number of high-...

TGIF1 is a multifunctional protein that represses TGF-β-activated transcription by interacting with Smad2-Smad4 complexes. We found that the complex structure of TGIF1-HD bound to the TGACA motif revealed a combined binding mode that involves the HD core and the major groove, on the one hand, and the amino-terminal (N-term) arm and the minor groove...

The development of the malaria parasite, Plasmodium falciparum, in the human erythrocyte, relies on phospholipid metabolism to fulfil the massive need for membrane biogenesis. Phosphatidylcholine (PC) is the most abundant phospholipid in Plasmodium membranes. PC biosynthesis is mainly ensured by the de novo Kennedy pathway that is considered as an...

The folding of staphylococcal nuclease (SNase) is known to proceed via a major intermediate in which the central OB sub-domain is folded and the C-terminal helical sub-domain is disordered. To identify the structural and energetic determinants of this folding free energy landscape we have examined in detail, using high pressure NMR, the consequence...

The most abundant N6-methyladenosine (m6A) modification on mRNAs is installed non-stoichiometrically across transcripts, with 5′ untranslated regions (5′ UTRs) being the least conductive. 5′ UTRs are essential for translation initiation, yet the molecular mechanisms orchestrated by m6A remain poorly understood. Here, we combined structural, biochem...

Translation initiation on structured mammalian mRNAs requires DHX29, a DExH protein that comprises a unique 534-aa-long N-terminal region (NTR) and a common catalytic DExH core. DHX29 binds to 40S subunits and possesses 40S-stimulated NTPase activity essential for its function. In the cryo-EM structure of DHX29-bound 43S preinitiation complexes, th...

In higher eukaryotes, the mRNA sequence in the direct vicinity of the start codon, called the Kozak sequence (CRCCaugG, where R is a purine), is known to influence the rate of the initiation process. However, the molecular basis underlying its role remains poorly understood. Here, we present the cryoelectron microscopy (cryo-EM) structures of mamma...

In eukaryotes, cap-dependent translation initiation represents one of the most complex processes along the mRNA translation regulation pathway. It results in the formation of several transient complexes involving over a dozen eukaryotic initiation factors (eIFs) and culminates in the accommodation of the start codon at the P-site of the small ribos...

During their life cycle Plasmodium species rely on phospholipids to build the membranes necessary for daughter cell development. Phosphatidylcholine and phosphatidylethanolamine together represent about 85% of total membrane lipids, and inhibition of their biosynthesis leads to parasite death. This chapter summarizes the current findings on the ess...

Neuroglobin is a globin present in the brain and retina of mammals. This hexacoordinated hemoprotein binds small diatomic molecules, albeit with lower affinity compared with other globins. We report here the resonance assignment of murine met-Neuroglobine, free and in complex with cyanide.

The effects of cavity-creating mutations on the structural flexibility, local and global stability and dynamics of the folded state of staphylococcal nuclease (SNase) were examined with NMR spectroscopy, MD simulations, H/D exchange and pressure perturbation. Effects on global thermodynamic stability correlated well with the number of heavy atoms i...