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| - | [[Image:1eym.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1eym.png|left|200px]] |
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| | {{STRUCTURE_1eym| PDB=1eym | SCENE= }} | | {{STRUCTURE_1eym| PDB=1eym | SCENE= }} |
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| - | '''FK506 BINDING PROTEIN MUTANT, HOMODIMERIC COMPLEX'''
| + | ===FK506 BINDING PROTEIN MUTANT, HOMODIMERIC COMPLEX=== |
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| - | ==Overview==
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| - | Chemically induced dimerization provides a general way to gain control over intracellular processes. Typically, FK506-binding protein (FKBP) domains are fused to a signaling domain of interest, allowing crosslinking to be initiated by addition of a bivalent FKBP ligand. In the course of protein engineering studies on human FKBP, we discovered that a single point mutation in the ligand-binding site (Phe-36 --> Met) converts the normally monomeric protein into a ligand-reversible dimer. Two-hybrid, gel filtration, analytical ultracentrifugation, and x-ray crystallographic studies show that the mutant (F(M)) forms discrete homodimers with micromolar affinity that can be completely dissociated within minutes by addition of monomeric synthetic ligands. These unexpected properties form the basis for a "reverse dimerization" regulatory system involving F(M) fusion proteins, in which association is the ground state and addition of ligand abolishes interactions. We have used this strategy to rapidly and reversibly aggregate fusion proteins in different cellular compartments, and to provide an off switch for transcription. Reiterated F(M) domains should be generally useful as conditional aggregation domains (CADs) to control intracellular events where rapid, reversible dissolution of interactions is required. Our results also suggest that dimerization is a latent property of the FKBP fold: the crystal structure reveals a remarkably complementary interaction between the monomer binding sites, with only subtle changes in side-chain disposition accounting for the dramatic change in quaternary structure.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10852943}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10852943 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10852943}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Ligand-reversible dimer]] | | [[Category: Ligand-reversible dimer]] |
| | [[Category: Rotamase]] | | [[Category: Rotamase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:40:32 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 02:13:09 2008'' |
Revision as of 23:13, 30 June 2008
Template:STRUCTURE 1eym
FK506 BINDING PROTEIN MUTANT, HOMODIMERIC COMPLEX
Template:ABSTRACT PUBMED 10852943
About this Structure
1EYM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A ligand-reversible dimerization system for controlling protein-protein interactions., Rollins CT, Rivera VM, Woolfson DN, Keenan T, Hatada M, Adams SE, Andrade LJ, Yaeger D, van Schravendijk MR, Holt DA, Gilman M, Clackson T, Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7096-101. PMID:10852943
Page seeded by OCA on Tue Jul 1 02:13:09 2008
Categories: Homo sapiens | Peptidylprolyl isomerase | Single protein | Adams, S E. | Andrade, L J. | Clackson, T. | Gilman, M. | Hatada, M. | Holt, D A. | Keenan, T. | Rivera, V M. | Rollins, C T. | Schravendijk, M R.van. | Woolfson, D N. | Yaeger, D. | Isomerase | Ligand-reversible dimer | Rotamase
