Home › Research › Biomarkers
Dimerization of the transmembrane domain of amyloid precursor protein is determined by residues around the γ-secretase cleavage sites
Yan Y, Xu TH, Harikumar KG, Miller LJ, Melcher K, Xu HE.. The Journal of biological chemistry, 2017-08-08
Topic: Brain proteins, microglia and lab models
One of the hallmarks of Alzheimer's disease is the formation of extracellular amyloid plaques that consist mainly of abnormally aggregated forms of amyloid β (Aβ) peptides. These peptides are generated by γ-secretase-catalyzed cleavage of a dimeric membrane-bound C-terminal fragment (C99) of the amyloid precursor protein. Although C99 homodimerization has been linked to Aβ production and changes in the aggregation-determining Aβ42/Aβ40 ratio, the motif through which C99 dimerizes has remained controversial. Here, we have used two independent assays to gain insight into C99 homodimerization in the context of the membrane of live cells: bioluminescence resonance energy transfer and Tango membrane protein-protein interaction assays, which were further confirmed by traditional pull-down assays. Our results indicate a four-amino acid region within the C99 transmembrane helix ( 43 TVIV 46 ) as well as its local secondary structure as critical determinants for homodimerization. These four amino acids are also a hot spot of familial Alzheimer's disease-linked mutations that both decrease C99 homodimerization and γ-secretase cleavage and alter the initial cleavage site to increase the Aβ42/40 ratio.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Yan, Y., Xu, T. H., Harikumar, K. G., Miller, L. J., Melcher, K., & Xu, H. E. (2017). Dimerization of the transmembrane domain of amyloid precursor protein is determined by residues around the γ-secretase cleavage sites. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m117.789669
Vancouver
Yan Y, Xu TH, Harikumar KG, Miller LJ, Melcher K, Xu HE. Dimerization of the transmembrane domain of amyloid precursor protein is determined by residues around the γ-secretase cleavage sites. The Journal of biological chemistry. 2017. doi:10.1074/jbc.m117.789669. PMID: 28790170.
BibTeX
@article{yan2017-28790170,
author = {Yan, Y. and Xu, T. H. and Harikumar, K. G. and Miller, L. J. and Melcher, K. and Xu, H. E.},
title = {{Dimerization of the transmembrane domain of amyloid precursor protein is determined by residues around the γ-secretase cleavage sites}},
journal = {The Journal of biological chemistry},
year = {2017},
doi = {10.1074/jbc.m117.789669},
pmid = {28790170},
url = {https://doi.org/10.1074/jbc.m117.789669}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Our results indicate a four-amino acid region within the C99 transmembrane helix ( 43 TVIV 46 ) as well as its local secondary structure as critical determinants for homodimerization.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of biological chemistry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28790170) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Biomarkers
Also tagged “transmembrane-domain”
3 studies in the library carry the topic tag “transmembrane-domain”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 3 tagged studies.