X-ray structure of the metastable SEPT14-SEPT7 coiled coil reveals a hendecad region crucial for heterodimerization

Autor(es)

Cavini, Italo A. ; Winter, Ashley J. ; Pereira, Humberto D'Muniz ; Woolfson, Derek N. ; Crump, Matthew P. ; Garratt, Richard C.

• Tipo de documento: Artigo Científico
• Fonte: ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY; v. 79, p. 14-pg., 2023-10-01.

Resumo

Septins are membrane-associated, GTP-binding proteins that are present in most eukaryotes. They polymerize to play important roles as scaffolds and/or diffusion barriers as part of the cytoskeleton. alpha-Helical coiled-coil domains are believed to contribute to septin assembly, and those observed in both human SEPT6 and SEPT8 form antiparallel homodimers. These are not compatible with their parallel heterodimeric organization expected from the current model for protofilament assembly, but they could explain the interfilament cross-bridges observed by microscopy. Here, the first structure of a heterodimeric septin coiled coil is presented, that between SEPT14 and SEPT7; the former is a SEPT6/SEPT8 homolog. This new structure is parallel, with two long helices that are axially shifted by a full helical turn with reference to their sequence alignment. The structure also has unusual knobs-into-holes packing of side chains. Both standard seven-residue (heptad) and the less common 11-residue (hendecad) repeats are present, creating two distinct regions with opposite supercoiling, which gives rise to an overall straight coiled coil. Part of the hendecad region is required for heterodimerization and therefore may be crucial for selective septin recognition. These unconventional sequences and structural features produce a metastable heterocomplex that nonetheless has enough specificity to promote correct protofilament assembly. For instance, the lack of supercoiling may facilitate unzipping and transitioning to the antiparallel homodimeric state. (AU)

• Processo FAPESP: 18/19992-7 - Estudos estruturais dos coiled-coils heteroméricos de septinas por espectroscopia de ressonância magnética nuclear e cristalografia de raios-X
• Beneficiário: Italo Augusto Cavini
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 22/00262-4 - Estudos estruturais de coiled-coils heteroméricos de septinas por espectroscopia de ressonância magnética nuclear de alta resolução
• Beneficiário: Italo Augusto Cavini
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 14/15546-1 - Septinas: estudos comparativos visando correlacionar estrutura e função
• Beneficiário: Richard Charles Garratt
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/02897-1 - Filamentos de septinas: estrutura, polimerização e atuação em patologias
• Beneficiário: Richard Charles Garratt
• Modalidade de apoio: Auxílio à Pesquisa - Temático