PDBsum entry 4wvr

Cell adhesion

PDB id: 4wvr

Contents

Protein chains

98 a.a.

Waters ×296

PDB id:

4wvr

Name:

Cell adhesion

Title:

Crystal structure of dscam1 ig7 domain, isoform 5

Structure:

Down syndrome cell adhesion molecule, isoform ak. Chain: a, b, c, d. Fragment: unp residues 617-713. Synonym: dscam1 ig7 domain, isoform 5. Engineered: yes

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: dscam1, dscam, cg17800, dmel_cg17800. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.95Å R-factor: 0.184 R-free: 0.223

Authors:

Q.Chen,Y.Yu,S.Li,L.Cheng

Key ref:

S.A.Li et al. (2016). Structural basis of Dscam1 homodimerization: Insights into context constraint for protein recognition. Sci Adv, 2, e1501118. PubMed id: 27386517 DOI: 10.1126/sciadv.1501118

Date:

07-Nov-14 Release date: 18-Nov-15

Protein chains

Q0E9H9  (Q0E9H9_DROME) -  Cell adhesion molecule Dscam1 from Drosophila melanogaster

Seq: 2016 a.a.

Struc: 98 a.a.*

* PDB and UniProt seqs differ at 48 residue positions (black crosses)

DOI no: 10.1126/sciadv.1501118

Sci Adv 2:e1501118 (2016)

PubMed id: 27386517

Structural basis of Dscam1 homodimerization: Insights into context constraint for protein recognition.

S.A.Li, L.Cheng, Y.Yu, Q.Chen.

ABSTRACT

The Drosophila neural receptor Dscam1 (Down syndrome cell adhesion molecule 1) plays an essential role in neuronal wiring and self-avoidance. Dscam1 potentially encodes 19,008 ectodomains through alternative RNA splicing and exhibits exquisite isoform-specific homophilic binding, which makes it an exceptional example for studying protein binding specificity. However, structural information on Dscam1 is limited, which hinders illumination of the mechanism of Dscam1 isoform-specific recognition. Whether different Dscam1 isoforms adopt the same dimerization mode remains a subject of debate. We present 12 Dscam1 crystal structures, provide direct evidence indicating that all isoforms adopt a conserved homodimer geometry in a modular fashion, identify two mechanisms for the Ig2 binding domain to dispel electrostatic repulsion during dimerization, decode Ig2 binding specificity by a central motif at its symmetry center, uncover the role of glycosylation in Dscam1 homodimerization, and find electrostatic potential complementarity to help define the binding region and the antiparallel binding mode. We then propose a concept that the context of a protein may set restrictions to regulate its binding specificity, which provides a better understanding of protein recognition.