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Publication Abstract from PubMed

Septins are an example of subtle molecular recognition whereby different paralogues must correctly assemble into functional filaments important for essential cellular events such as cytokinesis. Most possess C-terminal domains capable of forming coiled coils which are believed to be involved in filament formation and bundling. Here, we report an integrated structural approach which aims to unravel their architectural diversity and in so doing provide direct structural information for the coiled-coil regions of five human septins. Unexpectedly, we encounter dimeric structures presenting both parallel and antiparallel arrangements which are in consonance with molecular modelling suggesting that both are energetically accessible. These sequences therefore code for two metastable states of different orientations which employ different but overlapping interfaces. The antiparallel structures present a mixed coiled-coil interface, one side of which is dominated by a continuous chain of core hydrophilic residues. This unusual type of coiled coil could be used to expand the toolkit currently available to the protein engineer for the design of previously unforeseen coiled-coil based assemblies. Within a physiological context, our data provide the first atomic details related to the assumption that the parallel orientation is likely formed between septin monomers from the same filament whilst antiparallelism may participate in the widely described interfilament cross bridges necessary for higher order structures and thereby septin function.

Orientational Ambiguity in Septin Coiled Coils and its Structural Basis.,Leonardo DA, Cavini IA, Sala FA, Mendonca DC, Rosa HVD, Kumagai PS, Crusca E Jr, Valadares NF, Marques IA, Brandao-Neto J, Munte CE, Kalbitzer HR, Soler N, Uson I, Andre I, Araujo APU, D'Muniz Pereira H, Garratt RC J Mol Biol. 2021 Feb 24;433(9):166889. doi: 10.1016/j.jmb.2021.166889. PMID:33639214^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.