Premium
The crystal structure of amyloid precursor‐like protein 2 E2 domain completes the amyloid precursor protein family
Author(s) -
Roisman Laila C.,
Han Sen,
Chuei Mun Joo,
Connor Andrea R.,
Cappai Roberto
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201802315r
Subject(s) - amyloid precursor protein , amyloid (mycology) , chemistry , domain (mathematical analysis) , biochemistry of alzheimer's disease , β amyloid , amyloid β , medicine , alzheimer's disease , disease , inorganic chemistry , mathematical analysis , mathematics
ABSTRACT The amyloid precursor–like protein 2 (APLP2) molecule is a type I transmembrane protein that is crucial for survival, cell‐cell adhesion, neuronal development, myelination, cancer metastasis, modulation of metal, and glucose and insulin homeostasis. Moreover, the importance of the amyloid precursor protein (APP) family in biology and disease is very well known because of its central role in Alzheimer disease. In this study, we determined the crystal structure of the independently folded E2 domain of APLP2 and compared that with its paralogues APP and APLP2, demonstrating high overall structural similarities. The crystal structure of APLP2 E2 was solved as an antiparallel dimer, and analysis of the protein interfaces revealed a distinct mode of dimerization that differs from the previously reported dimerization of either APP or APLP1. Analysis of the APLP2 E2 metal binding sites suggested it binds zinc and copper in a similar manner to APP and APLP1. The structure of this key protein might suggest a relationship between the distinct mode of dimerization and its biologic functions.—Roisman, L. C., Han, S., Chuei, M. J., Connor, A. R., Cappai, R. The crystal structure of amyloid precursor‐like protein 2 E2 domain completes the amyloid precursor protein family. FASEB J. 33, 5076–5081 (2019). www.fasebj.org