1t6w
From Proteopedia
(New page: 200px<br /><applet load="1t6w" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t6w" /> '''RATIONAL DESIGN OF A CALCIUM-BINDING ADHESIO...) |
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| - | [[Image:1t6w.gif|left|200px]]<br /><applet load="1t6w" size=" | + | [[Image:1t6w.gif|left|200px]]<br /><applet load="1t6w" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''RATIONAL DESIGN OF A CALCIUM-BINDING ADHESION PROTEIN NMR, 20 STRUCTURES'''<br /> | '''RATIONAL DESIGN OF A CALCIUM-BINDING ADHESION PROTEIN NMR, 20 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Ca2+, "a signal of life and death", controls numerous cellular processes | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1T6W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1T6W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T6W OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Kearney, A.]] | [[Category: Kearney, A.]] | ||
| - | [[Category: Liu, Z | + | [[Category: Liu, Z R.]] |
| - | [[Category: Merwe, P | + | [[Category: Merwe, P A.van der.]] |
| - | [[Category: Urbauer, J | + | [[Category: Urbauer, J L.]] |
| - | [[Category: Wilkins, A | + | [[Category: Wilkins, A L.]] |
| - | [[Category: Yang, J | + | [[Category: Yang, J J.]] |
[[Category: Yang, W.]] | [[Category: Yang, W.]] | ||
[[Category: Ye, Y.]] | [[Category: Ye, Y.]] | ||
| Line 27: | Line 27: | ||
[[Category: nmr]] | [[Category: nmr]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:10:34 2008'' |
Revision as of 13:10, 21 February 2008
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RATIONAL DESIGN OF A CALCIUM-BINDING ADHESION PROTEIN NMR, 20 STRUCTURES
Overview
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.
About this Structure
1T6W is a Single protein structure of sequence from Rattus norvegicus with as ligand. Full crystallographic information is available from OCA.
Reference
Design of a calcium-binding protein with desired structure in a cell adhesion molecule., Yang W, Wilkins AL, Ye Y, Liu ZR, Li SY, Urbauer JL, Hellinga HW, Kearney A, van der Merwe PA, Yang JJ, J Am Chem Soc. 2005 Feb 23;127(7):2085-93. PMID:15713084
Page seeded by OCA on Thu Feb 21 15:10:34 2008
Categories: Rattus norvegicus | Single protein | Kearney, A. | Liu, Z R. | Merwe, P A.van der. | Urbauer, J L. | Wilkins, A L. | Yang, J J. | Yang, W. | Ye, Y. | CA | Calcium-binding protein | Cd2 | Design | Nmr
