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Orientational ambiguity in septin coiled coils and its structural basis

DOI: 10.1016/j.jmb.2021.166889 DOI Help

Authors: Diego A. Leonardo (University of São Paulo) , Italo A. Cavini (University of São Paulo) , Fernanda A. Sala (University of São Paulo; Brazilian Center for Research in Energy and Materials) , Deborah C. Mendonça (University of São Paulo) , Higor V. D. Rosa (University of São Paulo) , Patricia S. Kumagai (University of São Paulo) , Edson Crusca Jr (University of São Paulo; São Paulo State University) , Napoleao F. Valadares (University of Brasília) , Ivo A. Marques (University of São Paulo; Federal University of Goiás) , Jose Brandao-Neto (Diamond Light Source) , Claudia E. Munte (University of Regensburg) , Hans R. Kalbitzer (University of Regensburg) , Nicolas Soler (Molecular Biology Institute of Barcelona, IBMB) , Isabel Uson (Molecular Biology Institute of Barcelona, IBMB; Catalan Institution for Research and Advanced Studies, ICREA) , Ingemar André (Lund University) , Ana P. U. Araujo (University of São Paulo) , Humberto D'Muniz Pereira (University of São Paulo) , Richard C. Garratt (University of São Paulo)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Molecular Biology , VOL 254

State: Published (Approved)
Published: February 2021
Diamond Proposal Number(s): 6397 , 23570 , 25296

Abstract: 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.

Journal Keywords: coiled coil; septins; protein filament; mixed hydrophobic/hydrophilic interface; crystal structures

Subject Areas: Biology and Bio-materials


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

Added On: 01/03/2021 14:30

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)