PDBsum entry 5aea

Cell adhesion

PDB id: 5aea

Contents

Protein chains

100 a.a.

Ligands

FLC

Waters ×163

PDB id:

5aea

Name:

Cell adhesion

Title:

Crystal structure of human ncam domain 1

Structure:

Neural cell adhesion molecule 1. Chain: a, b. Fragment: unp residues 20-116. Synonym: n-cam-1, ncam-1, ncam domain 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.90Å R-factor: 0.174 R-free: 0.199

Authors:

M.Kvansakul,K.Griffiths,M.Foley

Key ref:

K.Griffiths et al. (2016). i-bodies, Human Single Domain Antibodies That Antagonize Chemokine Receptor CXCR4. J Biol Chem, 291, 12641-12657. PubMed id: 27036939 DOI: 10.1074/jbc.M116.721050

Date:

27-Aug-15 Release date: 13-Apr-16

Protein chains

P13591  (NCAM1_HUMAN) -  Neural cell adhesion molecule 1 from Homo sapiens

Seq: 858 a.a.

Struc: 100 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1074/jbc.M116.721050

J Biol Chem 291:12641-12657 (2016)

PubMed id: 27036939

i-bodies, Human Single Domain Antibodies That Antagonize Chemokine Receptor CXCR4.

K.Griffiths, O.Dolezal, B.Cao, S.K.Nilsson, H.B.See, K.D.Pfleger, M.Roche, P.R.Gorry, A.Pow, K.Viduka, K.Lim, B.G.Lu, D.H.Chang, T.Murray-Rust, M.Kvansakul, M.A.Perugini, C.Dogovski, M.Doerflinger, Y.Zhang, K.Parisi, J.L.Casey, S.D.Nuttall, M.Foley.

ABSTRACT

CXCR4 is a G protein-coupled receptor with excellent potential as a therapeutic target for a range of clinical conditions, including stem cell mobilization, cancer prognosis and treatment, fibrosis therapy, and HIV infection. We report here the development of a fully human single-domain antibody-like scaffold termed an "i-body," the engineering of which produces an i-body library possessing a long complementarity determining region binding loop, and the isolation and characterization of a panel of i-bodies with activity against human CXCR4. The CXCR4-specific i-bodies show antagonistic activity in a range of in vitro and in vivo assays, including inhibition of HIV infection, cell migration, and leukocyte recruitment but, importantly, not the mobilization of hematopoietic stem cells. Epitope mapping of the three CXCR4 i-bodies AM3-114, AM4-272, and AM3-523 revealed binding deep in the binding pocket of the receptor.