AI Article Synopsis

  • Structural studies of symmetric homo-oligomers are crucial for understanding their functions in biological processes like cell signaling and regulation.
  • The paper introduces a comprehensive algorithm for determining the structures of homo-oligomers based on subunit configurations, which evaluates all possible forms while ensuring consistency with experimental data.
  • Using this algorithm on the human phospholamban pentamer, researchers found a range of complex structures, highlighting the uncertainty in structural data and identifying the pentamer as the most probable oligomeric state.

Article Abstract

Structural studies of symmetric homo-oligomers provide mechanistic insights into their roles in essential biological processes, including cell signaling and cellular regulation. This paper presents a novel algorithm for homo-oligomeric structure determination, given the subunit structure, that is both complete, in that it evaluates all possible conformations, and data-driven, in that it evaluates conformations separately for consistency with experimental data and for quality of packing. Completeness ensures that the algorithm does not miss the native conformation, and being data-driven enables it to assess the structural precision possible from data alone. Our algorithm performs a branch-and-bound search in the symmetry configuration space, the space of symmetry axis parameters (positions and orientations) defining all possible C(n) homo-oligomeric complexes for a given subunit structure. It eliminates those symmetry axes inconsistent with intersubunit nuclear Overhauser effect (NOE) distance restraints and then identifies conformations representing any consistent, well-packed structure to within a user-defined similarity level. For the human phospholamban pentamer in dodecylphosphocholine micelles, using the structure of one subunit determined from a subset of the experimental NMR data, our algorithm identifies a diverse set of complex structures consistent with the nine intersubunit NOE restraints. The distribution of determined structures provides an objective characterization of structural uncertainty: backbone RMSD to the previously determined structure ranges from 1.07 to 8.85 A, and variance in backbone atomic coordinates is an average of 12.32 A(2). Incorporating vdW packing reduces structural diversity to a maximum backbone RMSD of 6.24 A and an average backbone variance of 6.80 A(2). By comparing data consistency and packing quality under different assumptions of oligomeric number, our algorithm identifies the pentamer as the most likely oligomeric state of phospholamban, demonstrating that it is possible to determine the oligomeric number directly from NMR data. Additional tests on a number of homo-oligomers, from dimer to heptamer, similarly demonstrate the power of our method to provide unbiased determination and evaluation of homo-oligomeric complex structures.

Download full-text PDF

Source
http://dx.doi.org/10.1002/prot.21091DOI Listing

Publication Analysis

Top Keywords

structure determination
8
symmetric homo-oligomers
8
search symmetry
8
symmetry configuration
8
configuration space
8
subunit structure
8
evaluates conformations
8
data algorithm
8
nmr data
8
algorithm identifies
8

Similar Publications

Experimental Spin State Determination of Iron(II) Complexes by Hirshfeld Atom Refinement.

Chemistry

December 2024

RWTH Aachen University: Rheinisch-Westfalische Technische Hochschule Aachen, Institute of Inorganic Chemistry, Landoltweg 1a, 52074, Aachen, GERMANY.

In this study, we present the first experimental determination of the spin state of transition metal complexes by using Hirshfeld Atom Refinement. For the demonstration, the two iron(II) complexes, (NH4)2Fe(SO4)2*6H2O and [Fe(pic)3]Cl2*EtOH were investigated. The method involves the refinement using wavefunctions of different spin multiplicity and comparison against experimental diffraction data by means of refinement indicators and residual electron density.

View Article and Find Full Text PDF

FLUORESCENCE DETECTION OF DNA/RNA G-QUADRUPLEXES (G4s) BY TWICE-AS-SMART LIGANDS.

ChemMedChem

December 2024

Universite de Dijon, Institut de Chimie Moleculaire, ICMUB CNRS UMR6302, 9, avenue Alain Savary, 21078, Dijon, FRANCE.

Fluorescence detection of DNA and RNA G-quadruplexes (G4s) is a very efficient strategy to assess not only the existence and prevalence of cellular G4s but also their relevance as targets for therapeutic interventions. Among the fluorophores used to this end, turn-on probes are the most interesting since their fluorescence is triggered only upon interaction with their G4 targets, which ensures a high sensitivity and selectivity of detection. We reported on a series of twice-as-smart G4 probes, which are both smart G4 ligands (whose structure is reorganized upon interaction with G4s) and smart fluorescent probes (whose fluorescence is turned on upon interaction with G4s).

View Article and Find Full Text PDF

Patterns of Social Connection Among Older Adults in England.

JAMA Netw Open

December 2024

Department of Behavioural Science and Health, Institute of Epidemiology and Health Care, University College London, London, United Kingdom.

Importance: Issues related to social connection are increasingly recognized as a global public health priority. However, there is a lack of a holistic understanding of social connection and its health impacts given that most empirical research focuses on a single or few individual concepts of social connection.

Objective: To explore patterns of social connection and their associations with health and well-being outcomes.

View Article and Find Full Text PDF

Butyrylcholinesterase plays an indispensable role in organisms, and its abnormal expression poses a significant threat to human health and safety, covering various aspects including liver-related diseases, diabetes, obesity, cardiovascular and cerebrovascular diseases, and neurodegenerative diseases. In addition, toxic substances such as organophosphorus and carbamate pesticides markedly inhibit BChE activity. BChE activity serves as a critical parameter for the clinical diagnosis of acute organophosphorus pesticide poisoning and the evaluation of organophosphorus and carbamate pesticide residues.

View Article and Find Full Text PDF

Foxing of Watercolor Paper and Environmental Control as Preventive Actions.

Chempluschem

December 2024

Nanyang Technological University, School of Chemistry, Chemical Engineering and Biotechnology, SINGAPORE.

In Singapore's hot and humid climate, watercolor papers are particularly prone to a paper oxidation issue known as foxing, which refers to the discoloration forming yellowish-brown stains on paper, changing the visual outcome of the watercolor artworks. This research investigates two most popular types of watercolor paper, made from 100% cotton and cotton-wood-pulp mixture. Foxing was generally categorized into two types: biotic and abiotic foxing caused by fungi activities and the presence of metallic contaminants catalytic fungi growth.

View Article and Find Full Text PDF

Want 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!