6MQK

Crystal Structure of GTPase Domain of Human Septin 12 in complex with GDP

Summary for 6MQK

• Entry DOI: 10.2210/pdb6mqk/pdb
• Descriptor: Septin-12, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: cytoskeleton component septin gtpase spermatogenesis, structural protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 138254.44

Authors

Castro, D.K.S.V.,Pereira, H.M.,Brandao-Neto, J.,Ulian, A.P.U.,Garratt, R.C. (deposition date: 2018-10-10, release date: 2019-11-20, Last modification date: 2023-10-11)

Primary citation

Castro, D.K.S.D.V.,da Silva, S.M.O.,Pereira, H.D.,Macedo, J.N.A.,Leonardo, D.A.,Valadares, N.F.,Kumagai, P.S.,Brandao-Neto, J.,Araujo, A.P.U.,Garratt, R.C.
A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface.
Iucrj, 7:462-479, 2020

PubMed Abstract: Human 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 GTPγS 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 α5', 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.

PubMed: 32431830
DOI: 10.1107/S2052252520002973

Experimental method

X-RAY DIFFRACTION (2.19 Å)