2L1Q
Solution structure of human Liver Expressed Antimicrobial Peptide 2
Summary for 2L1Q
| Entry DOI | 10.2210/pdb2l1q/pdb |
| Descriptor | Liver-expressed antimicrobial peptide 2 (1 entity in total) |
| Functional Keywords | polypeptide, disulfides, antimicrobial protein, leap-2 |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 4593.37 |
| Authors | Clark, R.J. (deposition date: 2010-08-03, release date: 2010-09-22, Last modification date: 2024-10-30) |
| Primary citation | Henriques, S.T.,Tan, C.C.,Craik, D.J.,Clark, R.J. Structural and functional analysis of human liver-expressed antimicrobial peptide 2. Chembiochem, 11:2148-2157, 2010 Cited by PubMed Abstract: Human liver-expressed antimicrobial peptide 2 (LEAP-2) is a cationic antimicrobial peptide (CAMP) believed to have a protective role against bacterial infection. Little is known about the structure-activity relationships of LEAP-2 or its mechanism of action. In this study we describe the structure of LEAP-2, analyze its interaction with model membranes, and relate them to the antimicrobial activity of the peptide. The structure of LEAP-2, determined by NMR spectroscopy, reveals a compact central core with disorder at the N and C termini. The core comprises a β-hairpin and a 3(10)- helix that are braced by disulfide bonds between Cys17-28 and Cys23-33 and further stabilized by a network of hydrogen bonds. Membrane-affinity studies show that LEAP-2 membrane binding is governed by electrostatic attractions, which are sensitive to ionic strength. Truncation studies show that the C-terminal region of LEAP-2 is irrelevant for membrane binding, whereas the N-terminal (hydrophobic domain) and core regions (cationic domain) are essential. Bacterial-growth-inhibition assays reveal that the antimicrobial activity of LEAP-2 correlates with membrane affinity. Interestingly, the native and reduced forms of LEAP-2 have similar membrane affinity and antimicrobial activities; this suggests that disulfide bonds are not essential for the bactericidal activity. This study reveals that LEAP-2 has a novel fold for a CAMP and suggests that although LEAP-2 exhibits antimicrobial activity under low-salt conditions, there is likely to be another physiological role for the peptide. PubMed: 20845358DOI: 10.1002/cbic.201000400 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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