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PDBsum entry 1yuk
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Cell adhesion
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PDB id
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1yuk
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References listed in PDB file
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Key reference
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Title
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The crystal structure of the plexin-Semaphorin-Integrin domain/hybrid domain/i-Egf1 segment from the human integrin beta2 subunit at 1.8-A resolution.
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Authors
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M.Shi,
K.Sundramurthy,
B.Liu,
S.M.Tan,
S.K.Law,
J.Lescar.
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Ref.
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J Biol Chem, 2005,
280,
30586-30593.
[DOI no: ]
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PubMed id
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Abstract
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Integrins are modular (alphabeta) heterodimeric proteins that mediate cell
adhesion and convey signals across the plasma membrane. Interdomain motions play
a key role in signal transduction by propagating structural changes through the
molecule, thus controlling the activation state and adhesive properties of the
integrin. We expressed a soluble fragment of the human integrin beta2 subunit
comprising the plexin-semaphorin-integrin domain (PSI)/hybrid domain/I-EGF1
fragment and present its crystal structure at 1.8-A resolution. The structure
reveals an elongated molecule with a rigid architecture stabilized by nine
disulfide bridges. The PSI domain is located centrally and participates in the
formation of extended interfaces with the hybrid domain and I-EGF1 domains,
respectively. The hybrid domain/PSI interface involves the burial of an Arg
residue, and contacts between PSI and I-EGF1 are mainly mediated by well
conserved Arg and Trp residues. Conservation of key interacting residues across
the various integrin beta subunits sequences suggests that our structure
represents a good model for the entire integrin family. Superposition with the
integrin beta3 receptor in its bent conformation suggests that an articulation
point is present at the linkage between its I-EGF1 and I-EGF2 modules and
underlines the importance of this region for the control of integrin-mediated
cell adhesion.
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Figure 4.
FIG. 4. A, superposition of the I-EGF1 domain (red, Protein
Data Bank code 1YUK [PDB]
, this work) with the I-EGF4 from integrin  [3] (blue, Protein Data
Bank code 1JV2 [PDB]
) and the EGF domain of P-selectin (turquoise, Protein Data Bank
code 1FSB [PDB]
). The disulfide bonds C3-C6 and C7-C8 are well conserved,
constraining the fold of the C-terminal part of the EGF module.
The cysteine bridge (C2-C4) is absent in the I-EGF1 domain.
Large conformational variations are observed between the
N-terminal ends of the three structures. The present I-EGF1
structure lacks strand 4 leaving its strand
3
unpaired (see text). B, schematic representation of the I-EGF1
structure of human integrin [2]. The three disulfide
bonds C1-C5, C3-C6, and C7-C8 are indicated. It should be noted
that the cysteines are numbered according to the typical
integrin-EGF domain with 8 cysteines; in this case, C2 and C4
are missing. The Arg and Leu residues that replace C2 and C4,
respectively, according to the published sequence alignment (17)
are in a yellow background.
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Figure 5.
FIG. 5. Interaction between domains. Buried water molecules
are represented by stars, and hydrogen bonds are represented by
broken lines. A, interactions at the hybrid domain (yellow) and
the PSI domain (green) interface: the invariant Arg86 residue is
located centrally making several polar contacts indicated by
broken lines. B, interactions at the PSI domain (green) and the
I-EGF1 domain (red) interface: residues taking part in the
interaction are labeled. Also labeled is the Ile^455 in the
I-EGF1 domain that may play an important role in the interaction
with the I-EGF2 domain.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2005,
280,
30586-30593)
copyright 2005.
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