6mqk | pdb_00006mqk
Crystal Structure of GTPase Domain of Human Septin 12 in complex with GDP
Structural highlights
Disease[SEP12_HUMAN] Non-syndromic male infertility due to sperm motility disorder. The disease is caused by mutations affecting the gene represented in this entry. Function[SEP12_HUMAN] Filament-forming cytoskeletal GTPase (By similarity). Involved in spermatogenesis. Involved in the morphogenesis of sperm heads and the elongation of sperm tails probably implicating the association with alpha- and beta-tubulins (PubMed:24213608). Forms a filamentous structure with SEPTIN7, SEPTIN6, SEPTIN2 and probably SEPTIN4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation (PubMed:25588830). May play a role in cytokinesis (Potential).[1] [2] Publication Abstract from PubMedHuman septins 3, 9 and 12 are the only members of a specific subgroup of septins that display several unusual features, including the absence of a C-terminal coiled coil. This particular subgroup (the SEPT3 septins) are present in rod-like octameric protofilaments but are lacking in similar hexameric assemblies, which only contain representatives of the three remaining subgroups. Both hexamers and octamers can self-assemble into mixed filaments by end-to-end association, implying that the SEPT3 septins may facilitate polymerization but not necessarily function. These filaments frequently associate into higher order complexes which associate with biological membranes, triggering a wide range of cellular events. In the present work, a complete compendium of crystal structures for the GTP-binding domains of all of the SEPT3 subgroup members when bound to either GDP or to a GTP analogue is provided. The structures reveal a unique degree of plasticity at one of the filamentous interfaces (dubbed NC). Specifically, structures of the GDP and GTPgammaS complexes of SEPT9 reveal a squeezing mechanism at the NC interface which would expel a polybasic region from its binding site and render it free to interact with negatively charged membranes. On the other hand, a polyacidic region associated with helix alpha5', the orientation of which is particular to this subgroup, provides a safe haven for the polybasic region when retracted within the interface. Together, these results suggest a mechanism which couples GTP binding and hydrolysis to membrane association and implies a unique role for the SEPT3 subgroup in this process. These observations can be accounted for by constellations of specific amino-acid residues that are found only in this subgroup and by the absence of the C-terminal coiled coil. Such conclusions can only be reached owing to the completeness of the structural studies presented here. A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface.,Castro DKSDV, da Silva SMO, Pereira HD, Macedo JNA, Leonardo DA, Valadares NF, Kumagai PS, Brandao-Neto J, Araujo APU, Garratt RC IUCrJ. 2020 Mar 28;7(Pt 3):462-479. doi: 10.1107/S2052252520002973. eCollection, 2020 May 1. PMID:32431830[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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