Related Experiment Video

Updated: Mar 25, 2026

Click-Chemistry Based Fluorometric Assay for Apolipoprotein N-acyltransferase from Enzyme Characterization to High-Throughput Screening
07:37

Click-Chemistry Based Fluorometric Assay for Apolipoprotein N-acyltransferase from Enzyme Characterization to High-Throughput Screening

Published on: May 13, 2020

2.4K

Structural characterization of ANGPTL8 (betatrophin) with its interacting partner lipoprotein lipase

Amnah Siddiqa1, Jamil Ahmad1, Amjad Ali2

  • 1Research Center for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.

Computational Biology and Chemistry
|February 25, 2016
PubMed

Insights

Angiopoietin-like protein 8 (ANGPTL8) structural modeling reveals its potential to inhibit Lipoprotein Lipase (LPL). This study provides the first 3D structure prediction of ANGPTL8, uncovering interactions that may regulate LPL activity.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Modeling

Background:

  • Angiopoietin-like protein 8 (ANGPTL8) is a secretory protein implicated in lipid metabolism and pancreatic beta-cell function.
  • Understanding ANGPTL8's structure is crucial for elucidating its mechanism of action and identifying binding partners.
  • Lipoprotein Lipase (LPL) plays a key role in lipid metabolism and is a potential interaction partner for ANGPTL8.

Purpose of the Study:

  • To predict the 3-dimensional (3D) structure of ANGPTL8 using multiple modeling approaches.
  • To investigate potential protein-protein interactions between ANGPTL8 and LPL.
  • To provide structural insights into the functional relationship between ANGPTL8 and LPL.

Main Methods:

  • Homology modeling, de-novo structure prediction, and hybrid approaches were employed for ANGPTL8 structure modeling.
  • Protein structure verification was performed using ERRATT, PROSA, Qmean, and Ramachandran plot analysis.
  • Protein-protein interaction analysis between ANGPTL8 and LPL was conducted using CPORT and HADDOCK servers.

Main Results:

  • The crystal structure of the iSH2 domain of PI3K p85β subunit (PDB: 3mtt) served as a suitable template for ANGPTL8 homology modeling.
  • Multiple non-covalent interactions were identified between the predicted ANGPTL8 structure and LPL.
  • Interactions involved LPL's lid, thrombospondin (TSP) region, and heparin-binding site, suggesting ANGPTL8's regulatory role in LPL proteolysis, motility, and localization.

Conclusions:

  • The study presents the first predicted 3D structure of ANGPTL8.
  • Results suggest ANGPTL8 inhibits LPL activity via steric hindrance at the catalytic site.
  • These findings provide a structural basis for future experimental validation of ANGPTL8-LPL interactions and regulatory mechanisms.
Keywords:
ANGPTL8BetatrophinComparative modelingLPLProtein structure

More Related Videos

Enrichment of Bacterial Lipoproteins and Preparation of N-terminal Lipopeptides for Structural Determination by Mass Spectrometry10:59

Enrichment of Bacterial Lipoproteins and Preparation of N-terminal Lipopeptides for Structural Determination by Mass Spectrometry

Published on: May 21, 2018

9.4K
Optimized Negative Staining: a High-throughput Protocol for Examining Small and Asymmetric Protein Structure by Electron Microscopy09:37

Optimized Negative Staining: a High-throughput Protocol for Examining Small and Asymmetric Protein Structure by Electron Microscopy

Published on: August 15, 2014

45.2K

Related Concept Videos

Lipids as Anchors01:32

Lipids as Anchors

In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
7.9K
Formation of Lipopolysaccharides01:19

Formation of Lipopolysaccharides

Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin,...
916
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
4.0K