2GW9

High-resolution solution structure of the mouse defensin Cryptdin4

Summary for 2GW9

• Entry DOI: 10.2210/pdb2gw9/pdb
• NMR Information: BMRB: 6264
• Descriptor: Defensin-related cryptdin 4 (1 entity in total)
• Functional Keywords: triple stranded beta sheet, beta hairpin, antibiotic
• Biological source: Mus musculus (house mouse)
• Cellular location: Secreted: P28311
• Total number of polymer chains: 1
• Total formula weight: 3771.61

Authors

Rosengren, K.J.,Craik, D.J.,Vogel, H.J.,Daly, N.L.,Ouellette, A.J. (deposition date: 2006-05-04, release date: 2006-07-25, Last modification date: 2024-11-20)

Primary citation

Rosengren, K.J.,Daly, N.L.,Fornander, L.M.,Shirafuji, Y.,Qu, X.,Vogel, H.J.,Ouellette, A.J.,Craik, D.J.
Structural and functional characterization of the conserved salt bridge in mammalian paneth cell alpha-defensins: solution structures of mouse CRYPTDIN-4 and (E15D)-CRYPTDIN-4.
J.Biol.Chem., 281:28068-28078, 2006

PubMed Abstract: alpha-Defensins are mediators of mammalian innate immunity, and knowledge of their structure-function relationships is essential for understanding their mechanisms of action. We report here the NMR solution structures of the mouse Paneth cell alpha-defensin cryptdin-4 (Crp4) and a mutant (E15D)-Crp4 peptide, in which a conserved Glu(15) residue was replaced by Asp. Structural analysis of the two peptides confirms the involvement of this Glu in a conserved salt bridge that is removed in the mutant because of the shortened side chain. Despite disruption of this structural feature, the peptide variant retains a well defined native fold because of a rearrangement of side chains, which result in compensating favorable interactions. Furthermore, salt bridge-deficient Crp4 mutants were tested for bactericidal effects and resistance to proteolytic degradation, and all of the variants had similar bactericidal activities and stability to proteolysis. These findings support the conclusion that the function of the conserved salt bridge in Crp4 is not linked to bactericidal activity or proteolytic stability of the mature peptide.

PubMed: 16857681
DOI: 10.1074/jbc.M604992200

Experimental method

SOLUTION NMR