6WPO

NMR Structure of HSP-4 antimicrobial peptide in presence of DPC-d38 micelles

Summary for 6WPO

• Entry DOI: 10.2210/pdb6wpo/pdb
• NMR Information: BMRB: 30746
• Descriptor: Hylaseptin-4 (1 entity in total)
• Functional Keywords: antimicrobial peptide, antimicrobial protein
• Biological source: Boana punctata (Polka-dot tree frog)
• Total number of polymer chains: 1
• Total formula weight: 2419.84

Authors

Verly, R.M.,Nunes, L.O. (deposition date: 2020-04-27, release date: 2021-03-17, Last modification date: 2024-10-30)

Primary citation

Nunes, L.O.,Munhoz, V.H.O.,Sousa, A.A.,de Souza, K.R.,Santos, T.L.,Bemquerer, M.P.,Ferreira, D.E.C.,de Magalhaes, M.T.Q.,Resende, J.M.,Alcantara, A.F.C.,Aisenbrey, C.,Veloso, D.P.,Bechinger, B.,Verly, R.M.
High-resolution structural profile of hylaseptin-4: Aggregation, membrane topology and pH dependence of overall membrane binding process.
Biochim Biophys Acta Biomembr, 1863:183581-183581, 2021

PubMed Abstract: Hylaseptin-4 (HSP-4, GIGDILKNLAKAAGKAALHAVGESL-NH) is an antimicrobial peptide originally isolated from Hypsiboas punctatus tree frog. The peptide has been chemically synthetized for structural investigations by CD and NMR spectroscopies. CD experiments reveal the high helical content of HSP-4 in biomimetic media. Interestingly, the aggregation process seems to occur at high peptide concentrations either in aqueous solution or in presence of biomimetic membranes, indicating an increase in the propensity of the peptide for adopting a helical conformation. High-resolution NMR structures determined in presence of DPC-d micelles show a highly ordered α-helix from amino acid residues I2 to S24 and a smooth bend near G14. A large separation between hydrophobic and hydrophilic residues occurs up to the A16 residue, from which a shift in the amphipathicity is noticed. Oriented solid-state NMR spectroscopy show a roughly parallel orientation of the helical structure along the POPC lipid bilayer surface, with an insertion of the hydrophobic N-terminus into the bilayer core. Moreover, a noticeable pH dependence of the aggregation process in both aqueous and in biomimetic membrane environments is attributed to a single histidine residue (H19). The protonation degree of the imidazole side-chain might help in modulating the peptide-peptide or peptide-lipid interactions. Finally, molecular dynamics simulations confirm the orientation and preferential helical conformation and in addition, show that HSP-4 tends to self-aggregate in order to stabilize its active conformation in aqueous or phospholipid bilayer environments.

PubMed: 33556358
DOI: 10.1016/j.bbamem.2021.183581

Experimental method

SOLUTION NMR