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| {{STRUCTURE_1a57| PDB=1a57 | SCENE= }} | | {{STRUCTURE_1a57| PDB=1a57 | SCENE= }} |
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| '''THE THREE-DIMENSIONAL STRUCTURE OF A HELIX-LESS VARIANT OF INTESTINAL FATTY ACID BINDING PROTEIN, NMR, 20 STRUCTURES'''
| | ===THE THREE-DIMENSIONAL STRUCTURE OF A HELIX-LESS VARIANT OF INTESTINAL FATTY ACID BINDING PROTEIN, NMR, 20 STRUCTURES=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_9655337}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 9655337 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_9655337}} |
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| ==About this Structure== | | ==About this Structure== |
| 1A57 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A57 OCA]. | | 1A57 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A57 OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Lipid transport]] | | [[Category: Lipid transport]] |
| [[Category: Lipocalin]] | | [[Category: Lipocalin]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 09:49:43 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 16:09:30 2008'' |
