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PDBsum entry 1cs6
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Cell adhesion
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PDB id
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1cs6
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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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The crystal structure of the ligand binding module of axonin-1/tag-1 suggests a zipper mechanism for neural cell adhesion.
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Authors
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J.Freigang,
K.Proba,
L.Leder,
K.Diederichs,
P.Sonderegger,
W.Welte.
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Ref.
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Cell, 2000,
101,
425-433.
[DOI no: ]
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PubMed id
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Abstract
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We have determined the crystal structure of the ligand binding fragment of the
neural cell adhesion molecule axonin-1/TAG-1 comprising the first four
immunoglobulin (Ig) domains. The overall structure of axonin-1(Ig1-4) is
U-shaped due to contacts between domains 1 and 4 and domains 2 and 3. In the
crystals, these molecules are aligned in a string with adjacent molecules
oriented in an anti-parallel fashion and their C termini perpendicular to the
string. This arrangement suggests that cell adhesion by homophilic axonin-1
interaction occurs by the formation of a linear zipper-like array in which the
axonin-1 molecules are alternately provided by the two apposed membranes. In
accordance with this model, mutations in a loop critical for the formation of
the zipper resulted in the loss of the homophilic binding capacity of axonin-1.
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Figure 1.
Figure 1. Domain Structure of the Neural Cell Adhesion
Molecule Axonin-1/TAG-1Axonin-1/TAG-1 is composed of six Ig
domains that are arranged in a contiguous string in the
N-terminal moiety. The C-terminal moiety of axonin-1/TAG-1
consists of four FnIII domains. A junctional decapeptide
enriched in glycine and proline is interposed between the sixth
Ig and the first FnIII domain. Axonin-1/TAG-1 is anchored to the
cell membrane by a glycosylphosphatidylinositol group (for a
detailed description: [13 and 38]). By domain deletion studies,
the binding sites for the interactions of axonin-1 with NgCAM
and NrCAM have been localized within the first four Ig domains (
[27 and 12]). The results of binding studies with ligand CAMs
and monoclonal antibodies further suggested that the first four
Ig domains of axonin-1 form a unit that is structurally and
functionally intact only when all for domains are present (
[27]).
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Figure 7.
Figure 7. A Model for Cell–Cell Adhesion Mediated by a
Zipper-like Linear Array of Axonin-1 Molecules Originating
Alternately from the Apposed MembranesThe crystal structure
suggests a zipper model as the basis for the homophilic
interaction of axonin-1 molecules involved in an adhesive
contact between the membranes of apposed cells. While monomeric
axonin-1 molecules are preferably in a backfolded,
“horseshoe”-like conformation ([27]), axonin-1 molecules
engaged in a homophilic cis-interaction are assumed to be in the
extended conformation. It is possible that in the backfolded
“horseshoe” conformation, the homophilic binding site in the
FnIII moiety is masked. This would ensure that the homophilic
site in the FnIII region is selectively active in crosslinking
axonin-1 molecules involved in a zipper.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2000,
101,
425-433)
copyright 2000.
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