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| {{STRUCTURE_1t6w| PDB=1t6w | SCENE= }} | | {{STRUCTURE_1t6w| PDB=1t6w | SCENE= }} |
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| '''RATIONAL DESIGN OF A CALCIUM-BINDING ADHESION PROTEIN NMR, 20 STRUCTURES'''
| | ===RATIONAL DESIGN OF A CALCIUM-BINDING ADHESION PROTEIN NMR, 20 STRUCTURES=== |
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| ==Overview==
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| Ca2+, "a signal of life and death", controls numerous cellular processes through interactions with proteins. An effective approach to understanding the role of Ca2+ is the design of a Ca2+-binding protein with predicted structural and functional properties. To design de novo Ca2+-binding sites in proteins is challenging due to the high coordination numbers and the incorporation of charged ligand residues, in addition to Ca2+-induced conformational change. Here, we demonstrate the successful design of a Ca2+-binding site in the non-Ca2+-binding cell adhesion protein CD2. This designed protein, Ca.CD2, exhibits selectivity for Ca2+ versus other di- and monovalent cations. In addition, La3+ (Kd 5.0 microM) and Tb3+ (Kd 6.6 microM) bind to the designed protein somewhat more tightly than does Ca2+ (Kd 1.4 mM). More interestingly, Ca.CD2 retains the native ability to associate with the natural target molecule. The solution structure reveals that Ca.CD2 binds Ca2+ at the intended site with the designed arrangement, which validates our general strategy for designing de novo Ca2+-binding proteins. The structural information also provides a close view of structural determinants that are necessary for a functional protein to accommodate the metal-binding site. This first success in designing Ca2+-binding proteins with desired structural and functional properties opens a new avenue in unveiling key determinants to Ca2+ binding, the mechanism of Ca2+ signaling, and Ca2+-dependent cell adhesion, while avoiding the complexities of the global conformational changes and cooperativity in natural Ca2+-binding proteins. It also represents a major achievement toward designing functional proteins controlled by Ca2+ binding.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15713084}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15713084 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15713084}} |
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| ==About this Structure== | | ==About this Structure== |
| 1T6W 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=1T6W OCA]. | | 1T6W 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=1T6W OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Design]] | | [[Category: Design]] |
| [[Category: Nmr]] | | [[Category: Nmr]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:36:26 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:43:29 2008'' |
