8G21

Reelin C-Terminal Region

Summary for 8G21

• Entry DOI: 10.2210/pdb8g21/pdb
• NMR Information: BMRB: 31073
• Descriptor: Reelin (1 entity in total)
• Functional Keywords: alzheimers disease, gag interaction, sugar binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 4225.88

Authors

Chandrahas, A.S.,Marino, C.,Arboleda-Velasquez, J.F. (deposition date: 2023-02-03, release date: 2023-05-31, Last modification date: 2024-05-15)

Primary citation

Lopera, F.,Marino, C.,Chandrahas, A.S.,O'Hare, M.,Villalba-Moreno, N.D.,Aguillon, D.,Baena, A.,Sanchez, J.S.,Vila-Castelar, C.,Ramirez Gomez, L.,Chmielewska, N.,Oliveira, G.M.,Littau, J.L.,Hartmann, K.,Park, K.,Krasemann, S.,Glatzel, M.,Schoemaker, D.,Gonzalez-Buendia, L.,Delgado-Tirado, S.,Arevalo-Alquichire, S.,Saez-Torres, K.L.,Amarnani, D.,Kim, L.A.,Mazzarino, R.C.,Gordon, H.,Bocanegra, Y.,Villegas, A.,Gai, X.,Bootwalla, M.,Ji, J.,Shen, L.,Kosik, K.S.,Su, Y.,Chen, Y.,Schultz, A.,Sperling, R.A.,Johnson, K.,Reiman, E.M.,Sepulveda-Falla, D.,Arboleda-Velasquez, J.F.,Quiroz, Y.T.
Resilience to autosomal dominant Alzheimer's disease in a Reelin-COLBOS heterozygous man.
Nat Med, 29:1243-1252, 2023

PubMed Abstract: We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.

PubMed: 37188781
DOI: 10.1038/s41591-023-02318-3

Experimental method

SOLUTION NMR