6PEK
Structure of Spastin Hexamer (Subunit A-E) in complex with substrate peptide
Summary for 6PEK
| Entry DOI | 10.2210/pdb6pek/pdb |
| EMDB information | 20327 |
| Descriptor | Spastin, substrate peptide, TYR-GLU-TYR-GLU-TYR-GLU-TYR-GLU, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | aaa+ atpase, microtubule severing, motor protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 276468.35 |
| Authors | Han, H.,Schubert, H.L.,McCullough, J.,Monroe, N.,Sundquist, W.I.,Hill, C.P. (deposition date: 2019-06-20, release date: 2019-12-04, Last modification date: 2024-03-20) |
| Primary citation | Han, H.,Schubert, H.L.,McCullough, J.,Monroe, N.,Purdy, M.D.,Yeager, M.,Sundquist, W.I.,Hill, C.P. Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation. J.Biol.Chem., 295:435-443, 2020 Cited by PubMed Abstract: Many members of the AAA+ ATPase family function as hexamers that unfold their protein substrates. These AAA unfoldases include spastin, which plays a critical role in the architecture of eukaryotic cells by driving the remodeling and severing of microtubules, which are cytoskeletal polymers of tubulin subunits. Here, we demonstrate that a human spastin binds weakly to unmodified peptides from the C-terminal segment of human tubulin α1A/B. A peptide comprising alternating glutamate and tyrosine residues binds more tightly, which is consistent with the known importance of glutamylation for spastin microtubule severing activity. A cryo-EM structure of the spastin-peptide complex at 4.2 Å resolution revealed an asymmetric hexamer in which five spastin subunits adopt a helical, spiral staircase configuration that binds the peptide within the central pore, whereas the sixth subunit of the hexamer is displaced from the peptide/substrate, as if transitioning from one end of the helix to the other. This configuration differs from a recently published structure of spastin from , which forms a six-subunit spiral without a transitioning subunit. Our structure resembles other recently reported AAA unfoldases, including the meiotic clade relative Vps4, and supports a model in which spastin utilizes a hand-over-hand mechanism of tubulin translocation and microtubule remodeling. PubMed: 31767681DOI: 10.1074/jbc.AC119.009890 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.2 Å) |
Structure validation
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