Structure and biochemical analysis of the heparin-induced E1 dimer of the amyloid precursor protein

Abstract

The authors note the following: "Due to an error in the evaluation of the raw ITC-data, we reported the wrong sign for the enthalpy values and correspondingly incorrect entropy values. The correct values are as follows: at pH 5.7: ΔH −54 ± 4 kJ/ mol, ΔS −68 ± 14 J/mol K and at pH 7.2: ΔH −62 ± 6 kJ/mol and ΔS −98 ± 18 J/mol K (Table 3)." The authors note that on page 5381, left column, first paragraph, line 9 "Two E1 entities dimerize upon their interaction with heparin, requiring 8-12 sugar rings to form the heparin-bridged APP-E1 dimer in an endothermic and pH-dependent process that is characterized by a low micromolar dissociation constant" should have read "Two E1 entities dimerize upon their interaction with heparin, requiring 8-12 sugar rings to form the heparin-bridged APP-E1 dimer in an exothermic and pH-dependent process that is characterized by a low micromolar dissociation constant." On page 5384, right column, third paragraph, line 23 "This reaction is driven by high entropy contributions of around 300 J/mol · K, probably resulting from the release of associated ions and water molecules upon heparin binding, as also observed for other heparin-binding proteins (reviewed, e.g., in ref. 39)" should have read "This reaction is driven by significant enthalpic contributions, probably arising from protein-protein interactions, also observed for other heparin-binding proteins (reviewed, e.g., in ref. 39)." This error does not affect the conclusions of the article.

Crystal structure of amyloid precursor-like protein 1 and heparin complex suggests a dual role of heparin in E2 dimerization

“…As illustrated in Fig. 3A, the binding (29), which harbors the other heparin binding site of the fulllength molecule.…”

“…Although the crystal structure of E1 has been solved, the structure of the heparin complex is not yet known (29). The contribution of E2 to the dimerization of APP and APLPs has been questioned by some studies that seem to suggest that the dimerization is primarily mediated through the E1 domain (17,29).…”

“…Heparin binding also induces the dimerization of the E1 domain (29). Although the crystal structure of E1 has been solved, the structure of the heparin complex is not yet known (29).…”

“…Although the crystal structure of E1 has been solved, the structure of the heparin complex is not yet known (29). The contribution of E2 to the dimerization of APP and APLPs has been questioned by some studies that seem to suggest that the dimerization is primarily mediated through the E1 domain (17,29). This is difficult to reconcile with our results at the structural level: E1 and E2 are separated by an unstructured domain of 100 amino acids; dimerization at the E1 domain is therefore unlikely to hinder E2 dimerization, even though the latter occurs in an antiparallel fashion.…”

The human β-amyloid precursor protein: biomolecular and epigenetic aspects

“…Indeed, cell-culture studies support the homo-or hetero-dimers formation of APP family members, and trans-dimerization has been shown to promote cell-cell adhesion (27). It has been further demonstrated that heparin binding to the E1 or E2 region would induce the formation of APP dimerization (28). Downstream of the E1 and E2 regions, a 'RHDS' motif in the extracellular domain of APP within the Aβ sequence also appears to promote cell adhesion ( Figure 1B).…”