2LLM

Structure of amyloid precursor protein's transmembrane domain

Summary for 2LLM

• Entry DOI: 10.2210/pdb2llm/pdb
• NMR Information: BMRB: 18080
• Descriptor: Amyloid beta A4 protein (1 entity in total)
• Functional Keywords: alzheimer's disease, protein fibril
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P05067
• Total number of polymer chains: 1
• Total formula weight: 4450.46

Authors

Nadezhdin, K.D.,Bocharova, O.V.,Bocharov, E.V.,Arseniev, A.S. (deposition date: 2011-11-15, release date: 2012-06-20, Last modification date: 2024-05-15)

Primary citation

Nadezhdin, K.D.,Bocharova, O.V.,Bocharov, E.V.,Arseniev, A.S.
Structural and dynamic study of the transmembrane domain of the amyloid precursor protein.
Acta Naturae, 3:69-76, 2011

PubMed Abstract: Alzheimer's disease affects people all over the world, regardless of nationality, gender or social status. An adequate study of the disease requires essential understanding of the molecular fundamentals of the pathogenesis. The amyloid β-peptide, which forms amyloid plaques in the brain of people with Alzheimer's disease, is the product of sequential cleavage of a single-span membrane amyloid precursor protein (APP). More than half of the APP mutations found to be associated with familial forms of Alzheimer's disease are located in its transmembrane domain. The pathogenic mutations presumably affect the structural-dynamic properties of the APP transmembrane domain by changing its conformational stability and/or lateral dimerization. In the present study, the structure and dynamics of the recombinant peptide corresponding to the APP fragment, Gln686-Lys726, which comprises the APP transmembrane domain with an adjacent N-terminal juxtamembrane sequence, were determined in the membrane mimetic environment composed of detergent micelles using NMR spectroscopy. The structure obtained in dodecylphosphocholine micelles consists of two α-helices: a short surface-associated juxtamembrane helix (Lys687-Asp694) and a long transmembrane helix (Gly700-Leu723), both connected via a mobile loop region. A minor bend of the transmembrane α-helix is observed near the paired residues Gly708-Gly709. A cholesterol-binding hydrophobic cavity is apparently formed under the loop region, where the juxtamembrane α-helix comes into contact with the membrane surface near the N-terminus of the transmembrane α-helix.

PubMed: 22649674

Experimental method

SOLUTION NMR