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PDB:1wuz

Protein Name

Neuronal cell adhesion protein protocadherin CNR

Species

House mouse (Mus musculus)

Biological Context

The recent explosion in genome sequencing has revealed the great diversity of the cadherin superfamily. Within the superfamily, protocadherins, which are mainly expressed in the nervous system, constitute the largest subgroup. Nevertheless, the structures of only the classical cadherins were known. Thus, to broaden the understanding of the cadherins' adhesive repertoire, the structure of the N-terminal first extracellular cadherin (EC1) domain of Cadherin-related Neuronal Receptor/Protocadherin alpha (CNR/Pcdh alpha4) has been determined.

For years, our understanding of the repertoire of adhesiveness in the cadherin superfamily was derived largely from studies of the classical cadherin subfamily. The structure reveals that the adhesive repertoire of the cadherin superfamily is far more divergent than would be predicted by studying the classical cadherins alone. Since the members of the protocadherin family are mainly expressed in the nervous system, their diverse structures and functional repertoire may be specifically required for the construction of the highly organized brain. Our study also paves the way for studies designed to reveal more about the molecular basis of the extraordinary diversity of brains.

Structure Description

1wuz1wuz_x1wuz_y

The EC1 domain of CNR/Pcdh alpha 4 has the Greek-key topology of a beta sandwich-like structure containing two beta sheets that are packed face to face. One sheet is composed of four beta strands, and the other of three beta strands. All the strands are arranged antiparallel, except for the parallel pairing between beta A and beta G. Three loops that are spatially close to the N terminus and three close to the C terminus connect the corresponding pairs of beta strands. The beta sandwich scaffold is stabilized by an extensive hydrogen bond network between neighboring beta strands and by a hydrophobic core formed by inward-facing residues from the beta sheets.

Despite low sequence similarities between the EC1 domains of CNR/Pcdh alpha 4 and the classical cadherins (37%), the overall topology of the CNR/Pcdh alpha 4-EC1 domain is similar to that of classical cadherin domains in that both contained seven beta strands, and the corresponding beta strands have similar lengths. However, the hydrophobic pocket essential for homophilic adhesiveness in the classical cadherins is not found (Fig.). Moreover, potentially crucial variations are observed mainly in the loop regions. These include the Protocadherin-specific disulfide bonded Cys-(X)5-Cys motif and the RGD motif, which has been suggested to be involved in heterophilic cell adhesion via the active form of beta 1 integrin.

Figure. Examples with or without the hydrophobic pocket required for homophilic adhesion.

Protein Data Bank (PDB)

References

Source

  • Morishita, H. Umitsu, M. Yamaguchi, T. Murata, Y. Shibata, N. Udaka, K. Higuchi, Y. Akutsu, H. Yagi, T. Ikegami, T.; "Structural diversity of the first cadherin domains revealed by the structure of CNR/Protocadherin alpha"; To be Published; () :-.

Others

author: Takahisa Ikegami


Japanese version:PDB:1wuz