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Biology subjects

VACCA, F.

Publications and source records attributed to VACCA, F..

2 recordsLinked to original sources

Characterization of Influenza A HA and NA Subtypes Using Protein Sequences

MotivationInfluenza is an infectious disease associated with excess human deaths. For influenza A virus (IAV), the surface antigens hemagglutinin (HA) and neuraminidase (NA) define the specific subtype. The high mutation rate of IAV can make clinical testing and assigning subtype after sequencing challenging. Accurate subtype classification is important for tracking circulating IAV strains that may impact human health. ResultsWe analyzed a large IAV protein sequence dataset with known HA and NA subtypes. Using logistic regression and random forest approaches, we identified a small set of subtype-associated amino acids, which were then used to develop a subtype characterization method with near-optimal accuracy. Further analysis indicated that signal sequence peptide variation and indels in HA and NA explained the unique combination of subtype-associated amino acids.

bioinformatics↗

Control of Guanine Exchange Factor Activity Using De Novo Designed Protein Inhibitors

Guanine Exchange Factors (GEF) of the Dbl family are the main activators of RhoA GTPases. GEF and GTPase activity is tightly regulated at the subcellular level with fast kinetics. Therefore, to fully understand the function of Dbl GEFs requires their study in living cells. Towards developing molecular tools that reversibly and rapidly modulate the activity of endogenous GEFs in living cells, here we developed a general platform for engineering inhibitors against members of the Dbl family of GEFs using generative protein design. Engineered proteins showed high affinity and remarkable specificity for the target GEFs and modulated GEF activity both in vitro and in cells. In a proof-of-principle example, a GEF inhibitor was coupled to a light-activated module, enabling the optogenetic control of its activity in cells. These findings show that generative protein design can create modulators of intracellular signaling and broaden the range of tools available for biological research.

cell biology↗