help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gralle, M.
Right arrow Articles by Ferreira, S. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gralle, M.
Right arrow Articles by Ferreira, S. T.

Biophys J, December 2002, p. 3513-3524, Vol. 83, No. 6

Solution Studies and Structural Model of the Extracellular Domain of the Human Amyloid Precursor Protein

Matthias Gralle,* Michelle M. Botelho,* Cristiano L. P. de Oliveira,dagger Iris Torriani,dagger Dagger and Sérgio T. Ferreira*Dagger

 *Department of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro RJ 21944-590, Brazil;  dagger Instituto de Física "Gleb Wataghin," Unicamp, Campinas SP 13084-971, Brazil; and  Dagger Laboratório Nacional de Luz Síncrotron (LNLS), Campinas SP 13084-9701, Brazil

The amyloid precursor protein (APP) is the precursor of the beta -amyloid peptide (Abeta ), which is centrally related to the genesis of Alzheimer's disease (AD). In addition, APP has been suggested to mediate and/or participate in events that lead to neuronal degeneration in AD. Despite the fact that various aspects of the cell biology of APP have been investigated, little information on the structure of this protein is available. In this work, the solution structure of the soluble extracellular domain of APP (sAPP, composing 89% of the amino acid residues of the whole protein) has been investigated through a combination of size-exclusion chromatography, circular dichroism, and synchrotron radiation small-angle x-ray scattering (SAXS) studies. sAPP is monomeric in solution (65 kDa obtained from SAXS measurements) and exhibits an anisometric molecular shape, with a Stokes radius of 39 or 51 Å calculated from SAXS or chromatographic data, respectively. The radius of gyration and the maximum molecular length obtained by SAXS were 38 Å and 130 Å, respectively. Analysis of SAXS data further allowed building a structural model for sAPP in solution. Circular dichroism data and secondary structure predictions based on the amino acid sequence of APP suggested that a significant fraction of APP (30% of the amino acid residues) is not involved in standard secondary structure elements, which may explain the elongated shape of the molecule recovered in our structural model. Possible implications of the structure of APP in ligand binding and molecular recognition events involved in the biological functions of this protein are discussed.

Biophys J, December 2002, p. 3513-3524, Vol. 83, No. 6
© 2002 by the Biophysical Society   0006-3495/02/12/3513/12  $2.00


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
M. G. Botelho, M. Gralle, C. L. P. Oliveira, I. Torriani, and S. T. Ferreira
Folding and Stability of the Extracellular Domain of the Human Amyloid Precursor Protein
J. Biol. Chem., September 5, 2003; 278(36): 34259 - 34267.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the Biophysical Society.