PDBsum entry 3k66

Cell adhesion

PDB id: 3k66

Contents

Protein chain

218 a.a. *

Waters ×75

* Residue conservation analysis

PDB id:

3k66

Name:

Cell adhesion

Title:

X-ray crystal structure of the e2 domain of c. Elegans apl-1

Structure:

Beta-amyloid-like protein. Chain: a. Fragment: e2 domain: unp residues 240-478. Engineered: yes

Source:

Caenorhabditis elegans. Nematode. Organism_taxid: 6239. Gene: apl-1, c42d8.8. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.70Å R-factor: 0.251 R-free: 0.299

Authors:

J.T.Hoopes,Y.Ha

Key ref:

J.T.Hoopes et al. (2010). Structural characterization of the E2 domain of APL-1, a Caenorhabditis elegans homolog of human amyloid precursor protein, and its heparin binding site. J Biol Chem, 285, 2165-2173. PubMed id: 19906646 DOI: 10.1074/jbc.M109.018432

Date:

08-Oct-09 Release date: 10-Nov-09

Protein chain

Q10651  (A4_CAEEL) -  Amyloid-beta-like protein from Caenorhabditis elegans

Seq: 686 a.a.

Struc: 218 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M109.018432

J Biol Chem 285:2165-2173 (2010)

PubMed id: 19906646

Structural characterization of the E2 domain of APL-1, a Caenorhabditis elegans homolog of human amyloid precursor protein, and its heparin binding site.

J.T.Hoopes, X.Liu, X.Xu, B.Demeler, E.Folta-Stogniew, C.Li, Y.Ha.

ABSTRACT

The amyloid beta-peptide deposit found in the brain tissue of patients with Alzheimer disease is derived from a large heparin-binding protein precursor APP. The biological function of APP and its homologs is not precisely known. Here we report the x-ray structure of the E2 domain of APL-1, an APP homolog in Caenorhabditis elegans, and compare it to the human APP structure. We also describe the structure of APL-1 E2 in complex with sucrose octasulfate, a highly negatively charged disaccharide, which reveals an unexpected binding pocket between the two halves of E2. Based on the crystal structure, we are able to map, using site-directed mutagenesis, a surface groove on E2 to which heparin may bind. Our biochemical data also indicate that the affinity of E2 for heparin is influenced by pH: at pH 5, the binding appears to be much stronger than that at neutral pH. This property is likely caused by histidine residues in the vicinity of the mapped heparin binding site and could be important for the proposed adhesive function of APL-1.

Selected figure(s)

Figure 2.
Structural comparison between APL-1 and APP. A, superposition of APP E2 (red: PDB entry 1rw6) onto the N-terminal subdomain of APL-1 E2 (black). The Cα traces are shown in stereo pairs. B, superposition of APP E2 (red: x-ray structure PDB entry 1rw6; green: NMR structure PDB entry 1tkn) onto the C-terminal subdomain of APL-1 E2 (black). These images were generated by Molscript (37).

Figure 5.
SOS was bound between the two halves of E2. A, binding site was near the middle of the molecule. B, detailed view of the sulfated glucose moiety of SOS, and its interactions with the protein. The six carbon atoms (C1–C6) of the glucose ring are labeled. The dotted lines represent hydrogen bonds. The side chain of Lys-372 is not visible in the electron density map, but its position on αD is indicated.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2010, 285, 2165-2173) copyright 2010.

Figures were selected by an automated process.