PDBsum entry 1mwp

Sugar binding protein

PDB id: 1mwp

Contents

Protein chain

96 a.a. *

Waters ×120

* Residue conservation analysis

PDB id:

1mwp

Name:

Sugar binding protein

Title:

N-terminal domain of the amyloid precursor protein

Structure:

Amyloid a4 protein. Chain: a. Fragment: heparin binding domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cell surface. Expressed in: pichia pastoris. Expression_system_taxid: 4922

Resolution:

1.80Å R-factor: 0.203 R-free: 0.242

Authors:

J.Rossjohn,R.Cappai,S.C.Feil,A.Henry,W.J.Mckinstry,D.Galatis,L.Hesse, G.Multhaup,K.Beyreuther,C.L.Masters,M.W.Parker

Key ref:

J.Rossjohn et al. (1999). Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein. Nat Struct Biol, 6, 327-331. PubMed id: 10201399 DOI: 10.1038/7562

Date:

09-Mar-99 Release date: 15-Mar-00

Protein chain

P05067  (A4_HUMAN) -  Amyloid-beta precursor protein from Homo sapiens

Seq: 770 a.a.

Struc: 96 a.a.

DOI no: 10.1038/7562

Nat Struct Biol 6:327-331 (1999)

PubMed id: 10201399

Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein.

J.Rossjohn, R.Cappai, S.C.Feil, A.Henry, W.J.McKinstry, D.Galatis, L.Hesse, G.Multhaup, K.Beyreuther, C.L.Masters, M.W.Parker.

ABSTRACT

Amyloid precursor protein (APP) plays a central role in Alzheimer disease. A proteolytic-breakdown product of APP, called beta-amyloid, is a major component of the diffuse and fibrillar deposits found in Alzheimer diseased brains. The normal physiological role of APP remains largely unknown despite much work. A knowledge of its function will not only provide insights into the genesis of the disease but may also prove vital in the development of an effective therapy. Here we describe the 1.8 A resolution crystal structure of the N-terminal, heparin-binding domain of APP (residues 28-123), which is responsible, among other things, for stimulation of neurite outgrowth. The structure reveals a highly charged basic surface that may interact with glycosaminoglycans in the brain and an abutting hydrophobic surface that is proposed to play an important functional role such as dimerization or ligand binding. Structural similarities with cysteine-rich growth factors, taken together with its known growth-promoting properties, suggests the APP N-terminal domain could function as a growth factor in vivo.

Selected figure(s)

Figure 1.
Figure 1. Structure of the APP N-terminal domain. a, A ribbon diagram indicating the location of secondary structure. Sheet A is colored blue, sheet B is in orange and sheet C is shown in brown. The disulfide bridges are shown in ball-and-stick, and the tip of the -hairpin loop is indicated. This figure was drawn with MOLSCRIPT^29. b, A stereo diagram of a C trace of the structure, shown in the same orientation as in (a), with every 20^th residue labeled. c, An orthogonal view drawn as a CPK representation. Basic residues are in blue, acidic residues in red, polar residues in pink and hydrophobic residues in green. The locations of key regions are highlighted. This figure was drawn with GRASP^30. d, Stereo 2F[o] - F[c] electron density map (blue), calculated using the final model, at 1.8 Å resolution. The map is contoured at 1 , with the final model overlaid upon it. The region shown corresponds to part of the hydrophobic core of the protein.

Figure 3.
Figure 3. Electrostatic surface representations^30 of APP family members. Blue indicates electropositive potential (> 10 kT) and red indicates electronegative potential (< -10 kT).

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 327-331) copyright 1999.

Figures were selected by the author.