Two polymorphs of an independent amyloid core in medin's C-terminal region.
- 1VIB & KU Leuven center for Neuroscience
Abstract
Medin, a 50-residue fragment of lactadherin (MFG-E8), forms aortic medial amyloid, the most common localized amyloid in humans, and co-deposits with vascular amyloid-{beta} (A{beta}) in Alzheimer's disease. In the full-length medin fibril the N-terminal half forms the entire protofilament interface, yet the strongest predicted amyloidogenic determinants lie in the C-terminal region. Here we show that this region aggregates on its own. The isolated C-terminal aggregation-prone region (medin C-APR, medin 31-53) begins to aggregate with the same lag time as full-length medin and assembles into two coexisting polymorphs, determined here by cryo-EM at 2.71 and 2.91 [A]. Both are built from the same two-stranded {beta}-arch and a pseudo-21 protofilament pair closed by an aromatic-aliphatic zipper, and differ only in how many accessory chains the exposed hydrophobic face recruits. The medin C-terminus therefore carries an amyloid core of its own, unrelated to that of the full-length fibril: medin has more than one aggregation-prone region, and the structural contribution of each region depends on sequence and assembly context.
Related
- The intrinsically disordered N-terminal region of eIF5B nucleates RNA-driven phase separation
- An N-terminal ATTR Fibril Segment Promotes Transthyretin Amyloid Nucleation and Polymorphism
- C-Terminal Regions of Insecticidal Cry Toxins Form Amyloid Fibrils Affecting Metabolism of Insect Cells.
- The DNA demethylase TET1 recognises chromatin via nucleosome engagement of its N-terminal region
- The N-Terminal Region of Drosophila MSL1 Interacts with Zinc Finger Proteins and Promotes the Recruitment of the MSL Complex to the X Chromosome in Males
BibTeX
@misc{pradhan2026polymorphs,
title = {{Two polymorphs of an independent amyloid core in medin's C-terminal region.}},
author = {B. Pradhan and F. Rousseau and J. Schymkowitz},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762820},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762820v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Two polymorphs of an independent amyloid core in medin's C-terminal region.
AU - B. Pradhan
AU - F. Rousseau
AU - J. Schymkowitz
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762820
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762820v1
AB - Medin, a 50-residue fragment of lactadherin (MFG-E8), forms aortic medial amyloid, the most common localized amyloid in humans, and co-deposits with vascular amyloid-{beta} (A{beta}) in Alzheimer's disease. In the full-length medin fibril the N-terminal half forms the entire protofilament interface, yet the strongest predicted amyloidogenic determinants lie in the C-terminal region. Here we show that this region aggregates on its own. The isolated C-terminal aggregation-prone region (medin C-APR, medin 31-53) begins to aggregate with the same lag time as full-length medin and assembles into two coexisting polymorphs, determined here by cryo-EM at 2.71 and 2.91 [A]. Both are built from the same two-stranded {beta}-arch and a pseudo-21 protofilament pair closed by an aromatic-aliphatic zipper, and differ only in how many accessory chains the exposed hydrophobic face recruits. The medin C-terminus therefore carries an amyloid core of its own, unrelated to that of the full-length fibril: medin has more than one aggregation-prone region, and the structural contribution of each region depends on sequence and assembly context.
ER -