PDBsum entry 1cs6

Cell adhesion

PDB id: 1cs6

Contents

Protein chain

382 a.a. *

Ligands

GOL

Waters ×357

* Residue conservation analysis

PDB id:

1cs6

Name:

Cell adhesion

Title:

N-terminal fragment of axonin-1 from chicken

Structure:

Axonin-1. Chain: a. Fragment: ig1-4. Engineered: yes

Source:

Gallus gallus. Chicken. Organism_taxid: 9031. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.80Å R-factor: 0.226 R-free: 0.257

Authors:

J.Freigang,K.Proba,K.Diederichs,P.Sonderegger,W.Welte

Key ref:

J.Freigang et al. (2000). The crystal structure of the ligand binding module of axonin-1/TAG-1 suggests a zipper mechanism for neural cell adhesion. Cell, 101, 425-433. PubMed id: 10830169 DOI: 10.1016/S0092-8674(00)80852-1

Date:

17-Aug-99 Release date: 19-May-00

Protein chain

P28685  (CNTN2_CHICK) -  Contactin-2 from Gallus gallus

Seq: 1036 a.a.

Struc: 382 a.a.

DOI no: 10.1016/S0092-8674(00)80852-1

Cell 101:425-433 (2000)

PubMed id: 10830169

The crystal structure of the ligand binding module of axonin-1/TAG-1 suggests a zipper mechanism for neural cell adhesion.

J.Freigang, K.Proba, L.Leder, K.Diederichs, P.Sonderegger, W.Welte.

ABSTRACT

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.

Selected figure(s)

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]).

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.

The above figures are reprinted by permission from Cell Press: Cell (2000, 101, 425-433) copyright 2000.

Figures were selected by an automated process.