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PDBsum entry 1hm6
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Metal, lipid binding protein
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PDB id
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1hm6
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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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X-Ray structure of full-Length annexin 1 and implications for membrane aggregation.
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Authors
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A.Rosengarth,
V.Gerke,
H.Luecke.
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Ref.
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J Mol Biol, 2001,
306,
489-498.
[DOI no: ]
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PubMed id
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Abstract
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Annexins comprise a multigene family of Ca2+ and phospholipid- binding proteins.
They consist of a conserved C-terminal or core domain that confers
Ca2+-dependent phospholipid binding and an N-terminal domain that is variable in
sequence and length and responsible for the specific properties of each annexin.
Crystal structures of various annexin core domains have revealed a high degree
of similarity. From these and other studies it is evident that the core domain
harbors the calcium-binding sites that interact with the phospholipid
headgroups. However, no structure has been reported of an annexin with a
complete N-terminal domain. We have now solved the crystal structure of such a
full-length annexin, annexin 1. Annexin 1 is active in membrane aggregation and
its refined 1.8 A structure shows an alpha-helical N-terminal domain connected
to the core domain by a flexible linker. It is surprising that the two
alpha-helices present in the N-terminal domain of 41 residues interact
intimately with the core domain, with the amphipathic helix 2-12 of the
N-terminal domain replacing helix D of repeat III of the core. In turn, helix D
is unwound into a flap now partially covering the N-terminal helix. Implications
for membrane aggregation will be discussed and a model of aggregation based on
the structure will be presented.
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Figure 1.
Figure 1. Ribbon diagrams of one monomer of (a) recombinant porcine annexin 1 comprising protein core and the
N-terminal domain and (b) human annexin 1 lacking the first 32 amino acid residues (delta1 to 32 anx I; PDB-code
1AIN).
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Repeat I is presented in red, repeat II in green, repeat III in blue, repeat IV in purple and the N-terminal
domain in yellow. The yellow N-terminal helix in (a) is replacing the two-turn blue helix in (b). Bound calcium ions
in delta1-32 annexin 1 are illustrated as yellow spheres. The Figure was prepared using MOLSCRIPT and
RASTER3D.
43,44
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Figure 3.
Figure 3. Stereo image of the 1.8 Å 3Fo
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2Fc electron density of the N-terminal domain and repeat III, contoured
at 1s. The backbone and side-chains are shown in gold. Met3, Val4 and Phe7 are located in a hydrophobic pocket
formed by residues Val220, Phe221, Ile224, Leu225 and Phe237 of repeat III. The Figure was prepared using
SETOR.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2001,
306,
489-498)
copyright 2001.
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Secondary reference #1
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Title
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Crystallization and preliminary X-Ray analysis of full-Length annexin i comprising the core and n-Terminal domain.
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Authors
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A.Rosengarth,
H.Luecke.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2000,
56,
1459-1461.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1 Mass spectra of dissolved annexin I crystals. The MALDI
technique was performed to prepare the protein sample using
3,5-dimethoxy-4-hydroxycinnamic acid as a matrix. The sample was
analyzed with the time-of-flight (TOF) mass spectrometer Voyager
DE-Pro (Perceptive Biosystems). The observed peaks reflect the
following annexin I species: m/z = 38 746.5, annexin I monomer
(calculated mass = 38 744 Da); m/z = 38 592.1, annexin
monomer minus the first methionine residue; m/z = 19 400.6 and
19 292.1; doubly charged species (m/z = 38 746.5 and 38
592.1, respectively); m/z = 35 693.6, annexin I derivative
lacking the first 26 amino acids.
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The above figure is
reproduced from the cited reference
with permission from the IUCr
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