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PDBsum entry 1oz4
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Transport protein
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PDB id
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1oz4
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Complete structure of p97/valosin-Containing protein reveals communication between nucleotide domains.
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Authors
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B.Delabarre,
A.T.Brunger.
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Ref.
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Nat Struct Biol, 2003,
10,
856-863.
[DOI no: ]
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PubMed id
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Abstract
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The ATPase p97/VCP affects multiple events within the cell. These events include
the alteration of both nuclear and mitotic Golgi membranes, the dislocation of
ubiquitylated proteins from the endoplasmic reticulum and regulation of the
NF-kappa b pathway. Here we present the crystal structure of full-length Mus
musculus p97/VCP in complex with a mixture of ADP and ADP-AlF(x) at a resolution
of 4.7 A. This is the first complete hexameric structure of a protein containing
tandem AAA (ATPases associated with a variety of cellular activities) domains.
Comparison of the crystal structure and cryo-electron microscopy (EM)
reconstructions reveals large conformational changes in the helical subdomains
during the hydrolysis cycle. Structural and functional data imply a
communication mechanism between the AAA domains. A Zn(2+) occludes the central
pore of the hexamer, suggesting that substrate does not thread through the pore
of the molecule.
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Figure 2.
Figure 2. p97/VCP protomer and pore schematic. (a,b) Two
orthogonal views of molecular surfaces of the p97/VCP hexamer,
with the subdomains of alternate protomers colored red or as in
Figure 1a. The Zn2+ and the putative His317 ligands are shown in
the central pore. Molecular dimensions are based on C  -C
distances,
with radii shown for the top view and diameters given for the
side view at the narrowest region in the middle and as well as
between opposing helices 12'.
(c) Schematic view of the pore with dimensions as indicated. The
protrusions shown within the D2 region of the pore indicate the
presence of a disordered section of the protein (residues 586
-597) that may point into the central pore. (d)
Protomer-protomer interactions. The 'A-facing' elements are
colored and labeled in red, the 'B-facing' elements are colored
according to subdomain. The view has been selected to highlight
the 'wrap-around' interaction involving helix 5/
5'.
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Figure 3.
Figure 3. Protomer views and schematic. (a,b) Orthogonal
views of the p97/VCP protomer with subdomains colored as in
Figure 1a. The disordered connection between 12'
and 13'
is indicated as a dashed green line. Selected helices are
labeled. (c) Schematic models of the p97/VCP protomer in the ADP
-AlF[x] and ADP states colored according to subdomain. The model
of the ADP state is derived from the comparison of the p97/VCP
crystal structure with the cryo-EM map of the ADP state^27; in
the ADP state the N-terminal domain is highly mobile and the
protrusion following helix 12'
of the D2 helical domain becomes ordered.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2003,
10,
856-863)
copyright 2003.
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