PDBsum entry 1epf

Cell adhesion

PDB id: 1epf

Contents

Protein chains

189 a.a. *

Metals

_CA

Waters ×1418

* Residue conservation analysis

PDB id:

1epf

Name:

Cell adhesion

Title:

Crystal structure of the two n-terminal immunoglobulin domains of the neural cell adhesion molecule (ncam)

Structure:

Protein (neural cell adhesion molecule). Chain: a, b, c, d. Fragment: n-terminal ig domain. Synonym: ncam. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

Biol. unit:

Dimer (from PQS)

Resolution:

1.85Å R-factor: 0.201 R-free: 0.234

Authors:

C.Kasper,H.Rasmussen,J.S.Kastrup,S.Ikemizu,E.Y.Jones,V.Berezin, E.Bock,I.K.Larsen

Key ref:

C.Kasper et al. (2000). Structural basis of cell-cell adhesion by NCAM. Nat Struct Biol, 7, 389-393. PubMed id: 10802736 DOI: 10.1038/75165

Date:

29-Mar-00 Release date: 09-Oct-00

Protein chains

P13596  (NCAM1_RAT) -  Neural cell adhesion molecule 1 from Rattus norvegicus

Seq: 858 a.a.

Struc: 189 a.a.

DOI no: 10.1038/75165

Nat Struct Biol 7:389-393 (2000)

PubMed id: 10802736

Structural basis of cell-cell adhesion by NCAM.

C.Kasper, H.Rasmussen, J.S.Kastrup, S.Ikemizu, E.Y.Jones, V.Berezin, E.Bock, I.K.Larsen.

ABSTRACT

The neural cell adhesion molecule NCAM, a member of the immunoglobulin superfamily, mediates cell-cell recognition and adhesion via a homophilic interaction. NCAM plays a key role during development and regeneration of the nervous system and is involved in synaptic plasticity associated with memory and learning. The 1.85 A crystal structure of the two N-terminal extracellular domains of NCAM reported here provides a structural basis for the homophilic interaction. The molecular packing of the two-domain structure reveals a cross shaped antiparallel dimer, and provides fundamental insight into trans-cellular recognition mediated by NCAM.

Selected figure(s)

Figure 1.
Figure 1. NCAM IgI-IgII structure and homophilic binding. a, Stereo view of the C trace of the two N-terminal immunoglobulin (Ig) domains of NCAM IgI-IgII. Every 10^th residue is labeled. Both domains belong to the I-type subfamily of Ig domains, and are tightly connected by a linker region of only two amino acids (Lys 98 and Leu 99) due to a long G strand in IgI. IgI consists of nine -strands whereas IgII contains only eight. The tilt angle between the domains is very small and this leads to an extended overall conformation. b,c, Ribbon diagram of the quaternary structure of the NCAM IgI-IgII dimer, using the A -B dimer as representative. b, Two IgI-IgII molecules form a cross shaped homodimer. Molecule A is shown in blue and molecule B in magenta with their individual domains labeled IgI and IgII. Two nearly symmetric interactions are formed in the dimer -- the residues forming interactions between IgI of molecule A and IgII of molecule B are virtually identical to those between IgII of molecule A and IgI of molecule B. IgII contains the putative heparin binding site of NCAM, and the loop bearing this sequence is shown in green. c, The dimer is rotated 90° around the vertical axis relative to the view in (b). This view shows the two salt bridge interactions between Glu 16 and Lys 98 in the linker region of molecule A and the corresponding residues in molecule B. The center of symmetry in the linker region is clear in this view. The Glu and Lys residues are colored according to atom types: carbon, green; nitrogen, blue and oxygen, red. d, Schematic representation of the mechanism of homophilic cell -cell adhesion mediated by NCAM based on the crystal structure. The cell surfaces are shown in black with NCAM protruding from them. The NCAM monomers, shown on the left, mediate adhesion by dimerization of IgI and IgII from opposite cells, as shown on the right. The two membrane proximal F3 domains are shown as green squares, and domains IgIII to IgV are depicted as pink and blue ovals, as the three-dimensional structures of these domains are not yet known. According to electron microscopy experiments there is a hinge region near IgV19, 22.

Figure 2.
Figure 2. The homophilic binding interface of NCAM. a, Space filling model of the interaction interface of the NCAM IgI-IgII dimer. To illustrate the complementarity of the residues in the two molecules, molecule A (blue) in the A -B dimer has been rotated 180° around the vertical axis, away from molecule B (pink), compared to Fig. 1b. Residues involved in homophilic binding are clustered near the IgI-IgII linker region, and these residues are color coded. Two salt bridges (Glu A16 -Lys B98 and vice versa) in the linker region (red) are surrounded by two patches of important residues, one in each of the IgI and IgII domains. Residues that participate in polar interactions (Ser 17, Thr 61, Thr 63, Arg 169, Glu 171, Arg 177, and Asn 181 in both molecules) are dark blue. Residues mainly involved in hydrophobic interactions (Val 6, cis Pro 7, Lys 18, Leu 175, Ala 176, Glu 179 and Phe 182 in both molecules) are green. The residues in yellow (Phe 19, Tyr 65, Arg 173, Gly 178 and Ile 180 in both molecules) participate in hydrophobic as well as polar interactions. b, Close up view of the interaction interface in the A -B dimer described in (a). Ribbon representations of -strands from molecule A and B are shown in transparent blue and pink, respectively. Residues involved in homophilic binding are represented as ball-and-stick models with carbon atoms from molecule A colored green, and residues from molecule B colored purple. A water molecule is shown as a red sphere. Red atoms indicate oxygen, and blue atoms nitrogen. At the dimer interface two conserved aromatic residues, Phe 19 and Tyr 65 from two opposite antiparallel strands in molecule A, intercalate into pockets created by a hairpin motif in molecule B. Phe 19 is shielded by hydrophobic interactions, whereas Tyr 65 participates in hydrophobic as well as polar interactions. Hydrogen bonds are shown as red dashed lines. c, Stereo view of the final 2F[o] - F[c] electron density map contoured at 1 level, showing the intercalation of Phe A19 into a pocket in molecule B made up of residues B173 -B178.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 389-393) copyright 2000.

Figures were selected by an automated process.