Molecular recognition at septin interfaces: the switches hold the key

Abstract

The assembly of a septin filament requires that homologous monomers must distinguish between one another in establishing appropriate interfaces with their neighbours. To understand this phenomenon at the molecular level, we present the first four crystal structures of heterodimeric septin complexes. We describe in detail the two distinct types of G-interface present within the octameric particles which must polymerize to form filaments. These are formed between SEPT2 and SEPT6 and between SEPT7 and SEPT3, and their description permits an understanding of the structural basis for the selectivity necessary for correct filament assembly. By replacing SEPT6 by SEPT8 or SEPT11, it is possible to rationalize Kinoshitas postulate which predicts the exchangeability of septins from within a subgroup. Switches I and II, which in classical small GTPases provide a mechanism for nucleotide-dependent conformational change, have been repurposed in septins to play a fundamental role in molecular recognition. Specifically, it is switch I which holds the key to discriminating between the two different G-interfaces. Moreover, residues which are characteristic for a given subgroup play subtle, but pivotal, roles in guaranteeing that the correct interfaces are formed. HIGHLIGHTSO_LIHigh resolution structures of septin heterodimeric complexes reveal new interactions C_LIO_LISwitches of small GTPases are repurposed in septins to play key roles in interface contacts C_LIO_LIThe GTP present in catalytically inactive septins participates in molecular recognition C_LIO_LIConservation of interface residues allows for subunit exchangeability from within septin subgroups C_LIO_LISpecific residues for each septin subgroup provide selectivity for proper filament assembly C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/161463v2_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@152f4daorg.highwire.dtl.DTLVardef@14936bdorg.highwire.dtl.DTLVardef@1a8f187org.highwire.dtl.DTLVardef@88d7f1_HPS_FORMAT_FIGEXP M_FIG C_FIG