1a57
From Proteopedia
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THE THREE-DIMENSIONAL STRUCTURE OF A HELIX-LESS VARIANT OF INTESTINAL FATTY ACID BINDING PROTEIN, NMR, 20 STRUCTURES
Overview
Intestinal fatty acid-binding protein (I-FABP) is a cytosolic 15.1-kDa, protein that appears to function in the intracellular transport and, metabolic trafficking of fatty acids. It binds a single molecule of, long-chain fatty acid in an enclosed cavity surrounded by two, five-stranded antiparallel beta-sheets and a helix-turn-helix domain. To, investigate the role of the helical domain, we engineered a variant of, I-FABP by deleting 17 contiguous residues and inserting a Ser-Gly linker, (Kim K et al., 1996, Biochemistry 35:7553-7558). This variant, termed, delta17-SG, was remarkably stable, exhibited a high beta-sheet content and, was able to bind fatty acids with some features characteristic of the, wild-type protein. In the present study, we determined the structure of, the delta17-SG/palmitate complex at atomic resolution using, triple-resonance 3D NMR methods. Sequence-specific 1H, 13C, and 15N, resonance assignments were established at pH 7.2 and 25 degrees C and used, to define the consensus 1H/13C chemical shift-derived secondary structure., Subsequently, an iterative protocol was used to identify 2,544 NOE-derived, interproton distance restraints and to calculate its tertiary structure, using a unique distance geometry/simulated annealing algorithm. In spite, of the sizable deletion, the delta17-SG structure exhibits a backbone, conformation that is nearly superimposable with the beta-sheet domain of, the wild-type protein. The selective deletion of the alpha-helical domain, creates a very large opening that connects the interior ligand-binding, cavity with exterior solvent. Unlike wild-type I-FABP, fatty acid, dissociation from delta17-SG is structurally and kinetically unimpeded, and a protein conformational transition is not required. The delta17-SG, variant of I-FABP is the only wild-type or engineered member of the, intracellular lipid-binding protein family whose structure lacks, alpha-helices. Thus, delta17-SG I-FABP constitutes a unique model system, for investigating the role of the helical domain in ligand-protein, recognition, protein stability and folding, lipid transfer mechanisms, and, cellular function.
About this Structure
1A57 is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
The three-dimensional structure of a helix-less variant of intestinal fatty acid-binding protein., Steele RA, Emmert DA, Kao J, Hodsdon ME, Frieden C, Cistola DP, Protein Sci. 1998 Jun;7(6):1332-9. PMID:9655337
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