LL-37 · research summary

Full-length brain-derived α-synuclein fibril models reveal fuzzy-coat control of peptide recognition.

Protein science : a publication of the Protein Society · 2026. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Computational reconstruction and simulation of alpha-synuclein fibrils
“Here, we reconstructed full‐length, brain‐derived aSyn Lewy‐fold fibrils by extending a patient‐derived cryo‐EM core spanning residues 31–100, with disordered termini, and sampling the resulting assemblies with the CALVADOS coarse‐grained force field.”

Subjects

Full-length, brain-derived alpha-synuclein Lewy-fold fibrils and binding peptides
“Simulations with two experimentally validated aSyn‐binding peptides, PSMα3 and LL‐37, show that peptide recognition follows a two‐step process.”

Reported findings

Acidic C-terminal tails form transient contacts with core motifs, creating a dynamic surface that intermittently shields aggregation-prone ladders
“The acidic C‐terminal tails established recurrent, transient contacts with solvent‐exposed core motifs, especially β5/P2 and β9/P3, generating a dynamic surface in which aggregation‐prone ladders are intermittently shielded rather than permanently buried.”
Peptide recognition involves a two-step process where cationic peptides are first retained by the anionic fuzzy coat before engaging core hotspots
“Cationic peptides are first retained by the anionic fuzzy coat and subsequently engage exposed hydrophobic/electrostatic hotspots on the structured core.”
Selectivity for aggregated alpha-synuclein arises from an emergent mesoscale interface combining a polyelectrolyte brush with recurrent core hotspots
“These results present a mechanistic model in which selectivity for aggregated aSyn arises from an emergent mesoscale interface combining a polyelectrolyte brush with recurrent core hotspots.”

Source: PubMed 42742050 · DOI 10.1002/pro.70782 · all study summaries

Study type

Computational reconstruction and simulation of alpha-synuclein fibrils

“Here, we reconstructed full‐length, brain‐derived aSyn Lewy‐fold fibrils by extending a patient‐derived cryo‐EM core spanning residues 31–100, with disordered termini, and sampling the resulting assemblies with the CALVADOS coarse‐grained force field.”

Reported findings

Acidic C-terminal tails form transient contacts with core motifs, creating a dynamic surface that intermittently shields aggregation-prone ladders

“The acidic C‐terminal tails established recurrent, transient contacts with solvent‐exposed core motifs, especially β5/P2 and β9/P3, generating a dynamic surface in which aggregation‐prone ladders are intermittently shielded rather than permanently buried.”

Peptide recognition involves a two-step process where cationic peptides are first retained by the anionic fuzzy coat before engaging core hotspots

“Cationic peptides are first retained by the anionic fuzzy coat and subsequently engage exposed hydrophobic/electrostatic hotspots on the structured core.”

Selectivity for aggregated alpha-synuclein arises from an emergent mesoscale interface combining a polyelectrolyte brush with recurrent core hotspots

“These results present a mechanistic model in which selectivity for aggregated aSyn arises from an emergent mesoscale interface combining a polyelectrolyte brush with recurrent core hotspots.”