Septins constitute a conserved guanine-binding protein family which are involved in several cellular processes and are capable of self-assembling into heterofilaments and high-order complexes. The human septins are encoded by 13 different genes and are divided into four groups based on their similarity. The C-terminal domain of septins contains characteristic repeats of alpha-helix coiled-coils whose importance in the formation and/or maintenance of complexes is still not fully understood. To date, the first and only crystallographic structure of a septin heterocomplex, the heterofilament SEPT2-6-7 published in 2007, does not contain information on the C-terminal domains - because of the absence of electron density in these regions. The current project proposes to obtain structural information on the C-terminal domains of SEPT6 (and others of its group as SEPT8, 10, 11 and 14) and SEPT7 using nuclear magnetic resonance and X-ray crystallography techniques. Among our objectives, we aim to determine interaction patterns that stabilize the interface of the SEPT6C-7C coiled-coil heterodimer and give selectivity to the heterofilament assembly. With nuclear magnetic resonance spectroscopy, we expect to obtain eNOEs, interproton distances up to 5 Å, that will indicate the relative orientation of the heterodimer and allow solving its structure in solution. In parallel, crystallographic assays will be performed to obtain a three-dimensional model also by X-ray diffraction. A better structural knowledge of the C-terminal domains will certainly shed light on how septins organize and also on the reason why different isoforms exist in some organisms.
News published in Agência FAPESP Newsletter about the scholarship: