5KZO
Notch1 transmembrane and associated juxtamembrane segment
Summary for 5KZO
| Entry DOI | 10.2210/pdb5kzo/pdb |
| NMR Information | BMRB: 30147 |
| Descriptor | Neurogenic locus notch homolog protein 1 (1 entity in total) |
| Functional Keywords | notch, membrane protein, transcription |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 6849.95 |
| Authors | Deatherage, C.L.,Lu, Z.,Kroncke, B. (deposition date: 2016-07-25, release date: 2017-05-10, Last modification date: 2024-05-01) |
| Primary citation | Deatherage, C.L.,Lu, Z.,Kroncke, B.M.,Ma, S.,Smith, J.A.,Voehler, M.W.,McFeeters, R.L.,Sanders, C.R. Structural and biochemical differences between the Notch and the amyloid precursor protein transmembrane domains. Sci Adv, 3:e1602794-e1602794, 2017 Cited by PubMed Abstract: γ-Secretase cleavage of the Notch receptor transmembrane domain is a critical signaling event for various cellular processes. Efforts to develop inhibitors of γ-secretase cleavage of the amyloid-β precursor C99 protein as potential Alzheimer's disease therapeutics have been confounded by toxicity resulting from the inhibition of normal cleavage of Notch. We present biochemical and structural data for the combined transmembrane and juxtamembrane Notch domains (Notch-TMD) that illuminate Notch signaling and that can be compared and contrasted with the corresponding traits of C99. The Notch-TMD and C99 have very different conformations, adapt differently to changes in model membrane hydrophobic span, and exhibit different cholesterol-binding properties. These differences may be exploited in the design of agents that inhibit cleavage of C99 while allowing Notch cleavage. PubMed: 28439555DOI: 10.1126/sciadv.1602794 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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