Primate cathelicidin orthologues display different structures and membrane interactions
Francesca Morgera1, Lisa Vaccari, Nikolinka Antcheva
1Department of Life Sciences, University of Trieste, 34127 Trieste, Italy. francesca.morgera@elettra.trieste.it
The Biochemical Journal
|October 17, 2008
Summary
Primate cathelicidin variations affect how peptides interact with cell membranes. Monomeric forms offer direct antibacterial action, while aggregated forms gain host-cell modulating functions.
Area of Science:
- Biophysics
- Biochemistry
- Molecular Biology
Background:
- Human cathelicidin LL-37 has antibacterial and host-cell modulating activities.
- Structural variations in primate cathelicidins, driven by positive selection, alter peptide properties.
- Differences in cationic/anionic residues affect salt-bridging, helical stability, and aggregation.
Purpose of the Study:
- To analyze the effects of structural variations on membrane interactions of human, rhesus (RL-37), and orangutan LL-37.
- To compare the biophysical and biochemical properties of different cathelicidin orthologues.
- To correlate structural states with antimicrobial and host-cell modulating functions.
Main Methods:
- Circular Dichroism (CD) spectroscopy
- Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy on model membranes
- Atomic Force Microscopy (AFM) on supported bilayers
Main Results:
- Rhesus RL-37 (monomeric, F-form) and human LL-37 (aggregated, A-form) exhibit distinct membrane binding modes.
- RL-37 may insert deeper into lipid bilayers, while LL-37 remains aggregated on the surface.
- AFM suggests RL-37 causes carpet-like permeabilization, whereas LL-37 forms worm-holes.
- Structural/aggregation state influences peptide trajectory and interaction with bacterial cell walls and membranes.
Conclusions:
- F-form cathelicidin orthologues (like RL-37) likely evolved for direct antimicrobial defense.
- A-form cathelicidins (like human LL-37) may have traded some antimicrobial potency for enhanced host-cell modulation.
- Structural variations are key to the divergent functional evolution of cathelicidin peptides.
More Related Videos
Related Concept Videos
Structure of Cadherins
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
Catenins
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Immunoglobulin-like Cell Adhesion Molecules
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Cadherins in Tissue Organization
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
Mechanisms of Membrane Domain Formation
Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with cytoskeletal...
Another mechanism for membrane domain formation involves membrane proteins interacting with cytoskeletal...
Membrane Domains
The membrane domains concentrate specific lipids and proteins at one place within the membrane, which helps in cell signaling, adhesion, and other critical cellular processes. These domains can differ in size, composition, function, and lifespan.
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the anterior...
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the anterior...


