Tracing the GSAP–APP C-99 Interaction Site in the β-Amyloid Pathway Leading to Alzheimer’s DiseaseCitation formats

  • Authors:
  • Deekshi Angira
  • Rupesh Chikhale
  • Kapilkumar Mehta
  • Richard A. Bryce
  • Vijay Thiruvenkatam

Standard

Tracing the GSAP–APP C-99 Interaction Site in the β-Amyloid Pathway Leading to Alzheimer’s Disease. / Angira, Deekshi; Chikhale, Rupesh; Mehta, Kapilkumar; Bryce, Richard A.; Thiruvenkatam, Vijay.

In: ACS Chemical Neuroscience, Vol. 10, No. 8, 21.08.2019, p. 3868-3879.

Research output: Contribution to journalArticlepeer-review

Harvard

Angira, D, Chikhale, R, Mehta, K, Bryce, RA & Thiruvenkatam, V 2019, 'Tracing the GSAP–APP C-99 Interaction Site in the β-Amyloid Pathway Leading to Alzheimer’s Disease', ACS Chemical Neuroscience, vol. 10, no. 8, pp. 3868-3879. https://doi.org/10.1021/acschemneuro.9b00332

APA

Angira, D., Chikhale, R., Mehta, K., Bryce, R. A., & Thiruvenkatam, V. (2019). Tracing the GSAP–APP C-99 Interaction Site in the β-Amyloid Pathway Leading to Alzheimer’s Disease. ACS Chemical Neuroscience, 10(8), 3868-3879. https://doi.org/10.1021/acschemneuro.9b00332

Vancouver

Angira D, Chikhale R, Mehta K, Bryce RA, Thiruvenkatam V. Tracing the GSAP–APP C-99 Interaction Site in the β-Amyloid Pathway Leading to Alzheimer’s Disease. ACS Chemical Neuroscience. 2019 Aug 21;10(8):3868-3879. https://doi.org/10.1021/acschemneuro.9b00332

Author

Angira, Deekshi ; Chikhale, Rupesh ; Mehta, Kapilkumar ; Bryce, Richard A. ; Thiruvenkatam, Vijay. / Tracing the GSAP–APP C-99 Interaction Site in the β-Amyloid Pathway Leading to Alzheimer’s Disease. In: ACS Chemical Neuroscience. 2019 ; Vol. 10, No. 8. pp. 3868-3879.

Bibtex

@article{2f0091c293e84769a49d7c36c60f622b,
title = "Tracing the GSAP–APP C-99 Interaction Site in the β-Amyloid Pathway Leading to Alzheimer{\textquoteright}s Disease",
abstract = "Gamma secretase activating protein (GSAP) present in β-amyloid pathway orchestrates the formation of β-amyloid plaques by γ-secretase activation and is an emerging therapeutic target for the treatment of Alzheimer{\textquoteright}s disease. It forms a ternary complex with γ-secretase and APP C-99. However, there are limited reports for the interaction of APP C-99 with GSAP. Here, we report the characterization of purified maltose binding protein (MBP) tagged human GSAP and its interaction with synthetic APP C-99 peptide fragments (712IATVIVITLVMLKKQ727 (712IQ727), 719TLVMLKKKQYTSIHHGVVEVDAAVT743 (719TT743) 734GVVEVDAAVTPEERHLSKMQQNGY757 (734GY757), and 746ERHLSKMQQNGYENPTYKFFEQMQN770 (746EN770)). The results emphasize the selective interaction of peptide (719TT743) with MBP-GSAP with a dissociation constant of 0.136 μM. Further, computational modeling of the GSAP–719TT743 complex finds an optimal bound pose of 719TT743 within an extended groove on the surface of GSAP. The preliminary results highlight the interaction between the two major proteins in the plausible ternary complex: APP C-99–GSAP−γ-secretase. It paves a futuristic path to investigate the GSAP–APP C-99 binding in detail and accentuates the role of GSAP in the β-amyloid pathway.",
author = "Deekshi Angira and Rupesh Chikhale and Kapilkumar Mehta and Bryce, {Richard A.} and Vijay Thiruvenkatam",
year = "2019",
month = aug,
day = "21",
doi = "10.1021/acschemneuro.9b00332",
language = "English",
volume = "10",
pages = "3868--3879",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "8",

}

RIS

TY - JOUR

T1 - Tracing the GSAP–APP C-99 Interaction Site in the β-Amyloid Pathway Leading to Alzheimer’s Disease

AU - Angira, Deekshi

AU - Chikhale, Rupesh

AU - Mehta, Kapilkumar

AU - Bryce, Richard A.

AU - Thiruvenkatam, Vijay

PY - 2019/8/21

Y1 - 2019/8/21

N2 - Gamma secretase activating protein (GSAP) present in β-amyloid pathway orchestrates the formation of β-amyloid plaques by γ-secretase activation and is an emerging therapeutic target for the treatment of Alzheimer’s disease. It forms a ternary complex with γ-secretase and APP C-99. However, there are limited reports for the interaction of APP C-99 with GSAP. Here, we report the characterization of purified maltose binding protein (MBP) tagged human GSAP and its interaction with synthetic APP C-99 peptide fragments (712IATVIVITLVMLKKQ727 (712IQ727), 719TLVMLKKKQYTSIHHGVVEVDAAVT743 (719TT743) 734GVVEVDAAVTPEERHLSKMQQNGY757 (734GY757), and 746ERHLSKMQQNGYENPTYKFFEQMQN770 (746EN770)). The results emphasize the selective interaction of peptide (719TT743) with MBP-GSAP with a dissociation constant of 0.136 μM. Further, computational modeling of the GSAP–719TT743 complex finds an optimal bound pose of 719TT743 within an extended groove on the surface of GSAP. The preliminary results highlight the interaction between the two major proteins in the plausible ternary complex: APP C-99–GSAP−γ-secretase. It paves a futuristic path to investigate the GSAP–APP C-99 binding in detail and accentuates the role of GSAP in the β-amyloid pathway.

AB - Gamma secretase activating protein (GSAP) present in β-amyloid pathway orchestrates the formation of β-amyloid plaques by γ-secretase activation and is an emerging therapeutic target for the treatment of Alzheimer’s disease. It forms a ternary complex with γ-secretase and APP C-99. However, there are limited reports for the interaction of APP C-99 with GSAP. Here, we report the characterization of purified maltose binding protein (MBP) tagged human GSAP and its interaction with synthetic APP C-99 peptide fragments (712IATVIVITLVMLKKQ727 (712IQ727), 719TLVMLKKKQYTSIHHGVVEVDAAVT743 (719TT743) 734GVVEVDAAVTPEERHLSKMQQNGY757 (734GY757), and 746ERHLSKMQQNGYENPTYKFFEQMQN770 (746EN770)). The results emphasize the selective interaction of peptide (719TT743) with MBP-GSAP with a dissociation constant of 0.136 μM. Further, computational modeling of the GSAP–719TT743 complex finds an optimal bound pose of 719TT743 within an extended groove on the surface of GSAP. The preliminary results highlight the interaction between the two major proteins in the plausible ternary complex: APP C-99–GSAP−γ-secretase. It paves a futuristic path to investigate the GSAP–APP C-99 binding in detail and accentuates the role of GSAP in the β-amyloid pathway.

U2 - 10.1021/acschemneuro.9b00332

DO - 10.1021/acschemneuro.9b00332

M3 - Article

VL - 10

SP - 3868

EP - 3879

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 8

ER -