Structural insights into the polymorphism of amyloid-like fibrils formed by region 20-29 of amylin revealed by solid-state NMR and X-ray fiber diffraction.

Many unrelated proteins and peptides can assemble into amyloid or amyloid-like nanostructures, all of which share the cross-beta motif of repeat arrays of beta-strands hydrogen-bonded along the fibril axis. Yet, paradoxically, structurally polymorphic fibrils may derive from the same initial polypeptide sequence. Here, solid-state nuclear magnetic resonance (SSNMR) analysis of amyloid-like fibrils of the peptide hIAPP 20-29, corresponding to the region S (20)NNFGAILSS (29) of the human islet amyloid polypeptide amylin, reveals that the peptide assembles into two amyloid-like forms, (1) and (2), which have distinct structures at the molecular level.

Membrane interactions of peptides representing the polybasic regions of three Rho GTPases are sensitive to the distribution of arginine and lysine residues.

Rho GTPases are a multifunctional family of proteins that are localized at cellular membranes via an isoprenyl group covalently linked to a C-terminal cysteine. Close to this primary site of membrane anchoring there is often found an additional polybasic region (PBR), which plays a secondary role in membrane binding and targeting of the complex. Here, peptides derived from the PBRs of the Rho family proteins Rac1 (K(183)KRKRK), TCL (K(198)KKKKR) and Cdc42 (P(182)KKSRR) were prepared with hexalysine (K(6)) and hexaarginine (R(6)) to study their interactions with multilamellar vesicles of phosphatidylglycerol (DOPG) and headgroup-deuterated dimyristoylphosphatidylcholine (DMPC-d(4)) using (2)H and (31)P NMR.

Apolipoprotein E-derived antimicrobial peptide analogues with altered membrane affinity and increased potency and breadth of activity.

Host-derived anti-infective proteins represent an important source of sequences for designing antimicrobial peptides (AMPs). However such sequences are often long and comprise diverse amino acids with uncertain contribution to biological effects. Previously, we identified a simple highly cationic peptide derivative of human apolipoprotein E (apoEdp) that inhibited a range of microorganisms.

The organization of aromatic side groups in an amyloid fibril probed by solid-state 2H and 19F NMR spectroscopy.

Some 25 diseases are associated with proteins and peptides that assemble into amyloid fibrils composed of beta-strands connected by hydrogen bonds oriented parallel to the fiber long axis. There is mounting evidence that amyloid formation involves specific interactions between amino acid side groups, which bring together beta-sheets to form layers with buried and exposed faces. This work demonstrates how a combination of solid-state 2H and 19F NMR experiments can provide constraints on fibril architecture by probing the environment and spatial organisation of aromatic side groups.