2hf5: Difference between revisions
New page: left|200px<br /> <applet load="2hf5" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hf5" /> '''The structure and function of a novel two-s... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2hf5. | [[Image:2hf5.jpg|left|200px]]<br /><applet load="2hf5" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2hf5" size=" | |||
caption="2hf5" /> | caption="2hf5" /> | ||
'''The structure and function of a novel two-site calcium-binding fragment of calmodulin'''<br /> | '''The structure and function of a novel two-site calcium-binding fragment of calmodulin'''<br /> | ||
| Line 6: | Line 5: | ||
==Overview== | ==Overview== | ||
Calmodulin (CaM) is an EF-hand protein composed of two calcium, (Ca(2+))-binding EF-hand motifs in its N-domain (EF-1 and EF-2) and two in, its C-domain (EF-3 and EF-4). In this study, we examined the structure, dynamics, and Ca(2+)-binding properties of a fragment of CaM containing, only EF-2 and EF-3 and the intervening linker sequence (CaM2/3). Based on, NMR spectroscopic analyses, Ca(2+)-free CaM2/3 is predominantly unfolded, but upon binding Ca(2+), adopts a monomeric structure composed of two, EF-hand motifs bridged by a short antiparallel beta-sheet. Despite having, an "even-odd" pairing of EF-hands, the tertiary structure of CaM2/3 is, similar to both the "odd-even" paired N- and C-domains of Ca(2+)-ligated, CaM, with the conformationally flexible linker sequence adopting the role, of an inter-EF-hand loop. However, unlike either CaM domain, CaM2/3, exhibits stepwise Ca(2+) binding with a K (d1) = 30 +/- 5 muM to EF-3, and, a K (d2) > 1000 muM to EF-2. Binding of the first equivalent of Ca(2+), induces the cooperative folding of CaM2/3. In the case of native CaM, stacking interactions between four conserved aromatic residues help to, hold the first and fourth helices of each EF-hand domain together, while, the loop between EF-hands covalently tethers the second and third helices., In contrast, these aromatic residues lie along the second and third, helices of CaM2/3, and thus are positioned adjacent to the loop between, its "even-odd" paired EF-hands. This nonnative hydrophobic core packing, may contribute to the weak Ca(2+) affinity exhibited by EF-2 in the, context of CaM2/3. | Calmodulin (CaM) is an EF-hand protein composed of two calcium, (Ca(2+))-binding EF-hand motifs in its N-domain (EF-1 and EF-2) and two in, its C-domain (EF-3 and EF-4). In this study, we examined the structure, dynamics, and Ca(2+)-binding properties of a fragment of CaM containing, only EF-2 and EF-3 and the intervening linker sequence (CaM2/3). Based on, NMR spectroscopic analyses, Ca(2+)-free CaM2/3 is predominantly unfolded, but upon binding Ca(2+), adopts a monomeric structure composed of two, EF-hand motifs bridged by a short antiparallel beta-sheet. Despite having, an "even-odd" pairing of EF-hands, the tertiary structure of CaM2/3 is, similar to both the "odd-even" paired N- and C-domains of Ca(2+)-ligated, CaM, with the conformationally flexible linker sequence adopting the role, of an inter-EF-hand loop. However, unlike either CaM domain, CaM2/3, exhibits stepwise Ca(2+) binding with a K (d1) = 30 +/- 5 muM to EF-3, and, a K (d2) > 1000 muM to EF-2. Binding of the first equivalent of Ca(2+), induces the cooperative folding of CaM2/3. In the case of native CaM, stacking interactions between four conserved aromatic residues help to, hold the first and fourth helices of each EF-hand domain together, while, the loop between EF-hands covalently tethers the second and third helices., In contrast, these aromatic residues lie along the second and third, helices of CaM2/3, and thus are positioned adjacent to the loop between, its "even-odd" paired EF-hands. This nonnative hydrophobic core packing, may contribute to the weak Ca(2+) affinity exhibited by EF-2 in the, context of CaM2/3. | ||
==About this Structure== | ==About this Structure== | ||
2HF5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 2HF5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=2HF5 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 28: | Line 24: | ||
[[Category: hlh]] | [[Category: hlh]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:47:20 2008'' | ||
Revision as of 15:47, 23 January 2008
|
The structure and function of a novel two-site calcium-binding fragment of calmodulin
OverviewOverview
Calmodulin (CaM) is an EF-hand protein composed of two calcium, (Ca(2+))-binding EF-hand motifs in its N-domain (EF-1 and EF-2) and two in, its C-domain (EF-3 and EF-4). In this study, we examined the structure, dynamics, and Ca(2+)-binding properties of a fragment of CaM containing, only EF-2 and EF-3 and the intervening linker sequence (CaM2/3). Based on, NMR spectroscopic analyses, Ca(2+)-free CaM2/3 is predominantly unfolded, but upon binding Ca(2+), adopts a monomeric structure composed of two, EF-hand motifs bridged by a short antiparallel beta-sheet. Despite having, an "even-odd" pairing of EF-hands, the tertiary structure of CaM2/3 is, similar to both the "odd-even" paired N- and C-domains of Ca(2+)-ligated, CaM, with the conformationally flexible linker sequence adopting the role, of an inter-EF-hand loop. However, unlike either CaM domain, CaM2/3, exhibits stepwise Ca(2+) binding with a K (d1) = 30 +/- 5 muM to EF-3, and, a K (d2) > 1000 muM to EF-2. Binding of the first equivalent of Ca(2+), induces the cooperative folding of CaM2/3. In the case of native CaM, stacking interactions between four conserved aromatic residues help to, hold the first and fourth helices of each EF-hand domain together, while, the loop between EF-hands covalently tethers the second and third helices., In contrast, these aromatic residues lie along the second and third, helices of CaM2/3, and thus are positioned adjacent to the loop between, its "even-odd" paired EF-hands. This nonnative hydrophobic core packing, may contribute to the weak Ca(2+) affinity exhibited by EF-2 in the, context of CaM2/3.
About this StructureAbout this Structure
2HF5 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Calcium-induced folding of a fragment of calmodulin composed of EF-hands 2 and 3., Lakowski TM, Lee GM, Okon M, Reid RE, McIntosh LP, Protein Sci. 2007 Jun;16(6):1119-32. Epub 2007 May 1. PMID:17473011
Page seeded by OCA on Wed Jan 23 14:47:20 2008