We present a structural model for amyloid fibrils formed by the 40-residue beta-amyloid peptide associated with Alzheimer's disease (Abeta(1-40)), based on a set of experimental constraints from solid state NMR spectroscopy. The model additionally incorporates the cross-beta structural motif established by x-ray fiber diffraction and satisfies constraints on Abeta(1-40) fibril dimensions and mass-per-length determined from electron microscopy. Approximately the first 10 residues of Abeta(1-40) are structurally disordered in the fibrils. Residues 12-24 and 30-40 adopt beta-strand conformations and form parallel beta-sheets through intermolecular hydrogen bonding. Residues 25-29 contain a bend of the peptide backbone that brings the two beta-sheets in contact through sidechain-sidechain interactions. A single cross-beta unit is then a double-layered beta-sheet structure with a hydrophobic core and one hydrophobic face. The only charged sidechains in the core are those of D23 and K28, which form salt bridges. Fibrils with minimum mass-per-length and diameter consist of two cross-beta units with their hydrophobic faces juxtaposed.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC139214 | PMC |
| http://dx.doi.org/10.1073/pnas.262663499 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A staged integrated model informing the promotion of healthy dietary behaviors in adolescents: a prospective study.
BMC Public Health
January 2025
Department of Health Behavior and Social Medicine, West China School of Public Health and West China Fourth Hospital, Research Center for Palliative Care, West China-PUMC C.C. Chen Institute of Health, Sichuan University, Chengdu, P.R. China.
Background: The promotion of healthy dietary behaviors in adolescence is critical, which have long-term implications for lifelong health. Integration is an important method for improving limited theories of dietary behavior change. The present study proposes an integrated model aimed at identifying the diverse determinants of healthy dietary behaviors in adolescents and assesses its stage-specific nature as the potential for effective interventions.
View Article and Find Full Text PDFThe two sides of Phobos: Gray and white matter abnormalities in phobic individuals.
Cogn Affect Behav Neurosci
January 2025
Departamento de Psicología ClínicaPsicobiología y MetodologíaFacultad de Psicología, Universidad de La Laguna, La Laguna, 38200, Tenerife, Spain.
Small animal phobia (SAP) is a subtype of specific phobia characterized by an intense and irrational fear of small animals, which has been underexplored in the neuroscientific literature. Previous studies often faced limitations, such as small sample sizes, focusing on only one neuroimaging modality, and reliance on univariate analyses, which produced inconsistent findings. This study was designed to overcome these issues by using for the first time advanced multivariate machine-learning techniques to identify the neural mechanisms underlying SAP.
View Article and Find Full Text PDFDifferential gray matter correlates and machine learning prediction of abuse and internalizing psychopathology in adolescent females.
Sci Rep
January 2025
Department of Psychiatry, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA.
Childhood abuse represents one of the most potent risk factors for the development of psychopathology during childhood, accounting for 30-60% of the risk for onset. While previous studies have separately associated reductions in gray matter volume (GMV) with childhood abuse and internalizing psychopathology (IP), it is unclear whether abuse and IP differ in their structural abnormalities, and which GMV features are related to abuse and IP at the individual level. In a pooled multisite, multi-investigator sample, 246 child and adolescent females between the ages of 8-18 were recruited into studies of interpersonal violence (IPV) and/or IP (i.
View Article and Find Full Text PDFHigh prevalence of alcohol use disorders in 454 young adult offspring from the San Diego prospective study.
Alcohol Clin Exp Res (Hoboken)
January 2025
Department of Psychiatry, University of California San Diego Medical School, San Diego, California, USA.
Background: Preliminary evaluations of 212 drinking offspring from the San Diego Prospective Study (SDPD) indicated that over 50% developed alcohol use disorder (AUD) by their mid-20s. The present analysis evaluated if those findings remained robust when the group increased to 454 individuals, a sample size that facilitated a search for potential contributors to the high AUD prevalence.
Methods: Semistructured interviews were used to evaluate lifetime AUD diagnoses in 224 daughters and 230 sons from the SDPS (N = 454) by mean age 26.
The Role of Machine Learning in the Detection of Cardiac Fibrosis in Electrocardiograms: Scoping Review.
JMIR Cardio
December 2024
School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada.
Background: Cardiovascular disease remains the leading cause of mortality worldwide. Cardiac fibrosis impacts the underlying pathophysiology of many cardiovascular diseases by altering structural integrity and impairing electrical conduction. Identifying cardiac fibrosis is essential for the prognosis and management of cardiovascular disease; however, current diagnostic methods face challenges due to invasiveness, cost, and inaccessibility.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!