4RDA

X-RAY STRUCTURE OF THE AMYLOID PRECURSOR PROTEIN-LIKE PROTEIN 1 (APLP1) E2 DOMAIN IN COMPLEX WITH A HEPARIN DODECASACCHARIDE

4RDA の概要

• エントリーDOI: 10.2210/pdb4rda/pdb
• 関連するPDBエントリー: 4RD9
• 分子名称: Amyloid-like protein 1, 4-deoxy-2-O-sulfo-alpha-L-threo-hex-4-enopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid, 2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid, ... (5 entities in total)
• 機能のキーワード: heparan sulfate binding, sugar binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. C30: Cytoplasm: P51693
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 52148.05

構造登録者

Dahms, S.O.,Than, M.E. (登録日: 2014-09-18, 公開日: 2015-03-11, 最終更新日: 2024-02-28)

主引用文献

Dahms, S.O.,Mayer, M.C.,Roeser, D.,Multhaup, G.,Than, M.E.
Interaction of the amyloid precursor protein-like protein 1 (APLP1) E2 domain with heparan sulfate involves two distinct binding modes.
Acta Crystallogr.,Sect.D, 71:494-504, 2015

PubMed Abstract: Beyond the pathology of Alzheimer's disease, the members of the amyloid precursor protein (APP) family are essential for neuronal development and cell homeostasis in mammals. APP and its paralogues APP-like protein 1 (APLP1) and APP-like protein 2 (APLP2) contain the highly conserved heparan sulfate (HS) binding domain E2, which effects various (patho)physiological functions. Here, two crystal structures of the E2 domain of APLP1 are presented in the apo form and in complex with a heparin dodecasaccharide at 2.5 Å resolution. The apo structure of APLP1 E2 revealed an unfolded and hence flexible N-terminal helix αA. The (APLP1 E2)2-(heparin)2 complex structure revealed two distinct binding modes, with APLP1 E2 explicitly recognizing the heparin terminus but also interacting with a continuous heparin chain. The latter only requires a certain register of the sugar moieties that fits to a positively charged surface patch and contributes to the general heparin-binding capability of APP-family proteins. Terminal binding of APLP1 E2 to heparin specifically involves a structure of the nonreducing end that is very similar to heparanase-processed HS chains. These data reveal a conserved mechanism for the binding of APP-family proteins to HS and imply a specific regulatory role of HS modifications in the biology of APP and APP-like proteins.

PubMed: 25760599
DOI: 10.1107/S1399004714027114

実験手法

X-RAY DIFFRACTION (2.497 Å)