PDBsum entry 2nd8

Lipid binding protein

PDB id: 2nd8

Contents

Protein chain

17 a.a.

PDB id:

2nd8

Name:

Lipid binding protein

Title:

Structures of dk17 in tble luvs

Structure:

Cell penetrating peptide. Chain: a. Engineered: yes

Source:

Synthetic: yes. Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Other_details: synthetic peptide, modified version of penetratin peptide, derived from antennapedia homeodomain protein (3rd helix) of drosophila melanogaster

NMR struc:

20 models

Authors:

S.Bera,A.Bhunia

Key ref:

S.Bera et al. (2016). Structural Elucidation of the Cell-Penetrating Penetratin Peptide in Model Membranes at the Atomic Level: Probing Hydrophobic Interactions in the Blood-Brain Barrier. Biochemistry, 55, 4982-4996. PubMed id: 27532224

Date:

11-May-16 Release date: 22-Mar-17

Protein chain

P02833  (ANTP_DROME) -  Homeotic protein antennapedia from Drosophila melanogaster

Seq: 378 a.a.

Struc: 17 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

Biochemistry 55:4982-4996 (2016)

PubMed id: 27532224

Structural Elucidation of the Cell-Penetrating Penetratin Peptide in Model Membranes at the Atomic Level: Probing Hydrophobic Interactions in the Blood-Brain Barrier.

S.Bera, R.K.Kar, S.Mondal, K.Pahan, A.Bhunia.

ABSTRACT

Cell-penetrating peptides (CPPs) have shown promise in nonpermeable therapeutic drug delivery, because of their ability to transport a variety of cargo molecules across the cell membranes and their noncytotoxicity. Drosophila antennapedia homeodomain-derived CPP penetratin (RQIKIWFQNRRMKWKK), being rich in positively charged residues, has been increasingly used as a potential drug carrier for various purposes. Penetratin can breach the tight endothelial network known as the blood-brain barrier (BBB), permitting treatment of several neurodegenerative maladies, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. However, a detailed structural understanding of penetratin and its mechanism of action is lacking. This study defines structural features of the penetratin-derived peptide, DK17 (DRQIKIWFQNRRMKWKK), in several model membranes and describes a membrane-induced conformational transition of the DK17 peptide in these environments. A series of biophysical experiments, including high-resolution nuclear magnetic resonance spectroscopy, provides the three-dimensional structure of DK17 in different membranes mimicking the BBB or total brain lipid extract. Molecular dynamics simulations support the experimental results showing preferential binding of DK17 to particular lipids at atomic resolution. The peptide conserves the structure of the subdomain spanning residues Ile6-Arg11, despite considerable conformational variation in different membrane models. In vivo data suggest that the wild type, not a mutated sequence, enters the central nervous system. Together, these data highlight important structural and functional attributes of DK17 that could be utilized in drug delivery for neurodegenerative disorders.