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New page: left|200px<br /> <applet load="1don" size="450" color="white" frame="true" align="right" spinBox="true" caption="1don" /> '''SOLUTION STRUCTURE OF THE MONOCYTE CHEMOATT...
 
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'''SOLUTION STRUCTURE OF THE MONOCYTE CHEMOATTRACTANT PROTEIN-1 DIMER USING HETERONUCLEAR, NMR, 20 STRUCTURES'''<br />
'''SOLUTION STRUCTURE OF THE MONOCYTE CHEMOATTRACTANT PROTEIN-1 DIMER USING HETERONUCLEAR, NMR, 20 STRUCTURES'''<br />


==Overview==
==Overview==
A full high-resolution three-dimensional solution structure of the, monocyte chemoattractant protein-1 (MCP-1 or MCAF) homodimer has been, determined by heteronuclear multidimensional NMR. MCP-1 is a member of a, family of small proteins which play a crucial role in immune surveillance, by orchestrating the recruitment of specific leukocytes to areas of immune, challenge. The protein was uniformly isotopically enriched with 13C and, 15N by expression in Escherichia coli, and complete sequence-specific, resonance assignments were obtained by a combination of heteronuclear, double- and triple-resonance experiments. The secondary structure was, deduced from characteristic patterns of NOEs, 13 C alpha/beta chemical, shifts, measurements of 3JHNH alpha scalar couplings, and patterns of, slowly exchanging amide protons. Because MCP-1 forms symmetrical, homodimers, additional experiments were carried out to unambiguously, establish the quaternary contacts. NOEs from these novel experiments were, merged with more traditional heteronuclear separated NOE measurements in, an iterative strategy to partition the restraints between explicit, inter/intrasubunit contacts and a class wherein both were retained as, ambiguous. With more than 30 restraints per residue, the three-dimensional, structure is well-defined with a backbone rmsd of 0.37 A to the mean over, residues 5-69 of the dimer. We compare the structure with those recently, reported for the related chemokines MIP-1 beta and RANTES and highlight, the differences in terms of receptor specificity and function as well as, interpret the known biological activity data of MCP-1 mutants.
A full high-resolution three-dimensional solution structure of the monocyte chemoattractant protein-1 (MCP-1 or MCAF) homodimer has been determined by heteronuclear multidimensional NMR. MCP-1 is a member of a family of small proteins which play a crucial role in immune surveillance by orchestrating the recruitment of specific leukocytes to areas of immune challenge. The protein was uniformly isotopically enriched with 13C and 15N by expression in Escherichia coli, and complete sequence-specific resonance assignments were obtained by a combination of heteronuclear double- and triple-resonance experiments. The secondary structure was deduced from characteristic patterns of NOEs, 13 C alpha/beta chemical shifts, measurements of 3JHNH alpha scalar couplings, and patterns of slowly exchanging amide protons. Because MCP-1 forms symmetrical homodimers, additional experiments were carried out to unambiguously establish the quaternary contacts. NOEs from these novel experiments were merged with more traditional heteronuclear separated NOE measurements in an iterative strategy to partition the restraints between explicit inter/intrasubunit contacts and a class wherein both were retained as ambiguous. With more than 30 restraints per residue, the three-dimensional structure is well-defined with a backbone rmsd of 0.37 A to the mean over residues 5-69 of the dimer. We compare the structure with those recently reported for the related chemokines MIP-1 beta and RANTES and highlight the differences in terms of receptor specificity and function as well as interpret the known biological activity data of MCP-1 mutants.


==Disease==
==Disease==
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==About this Structure==
==About this Structure==
1DON is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1DON OCA].  
1DON is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DON OCA].  


==Reference==
==Reference==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Domaille, P.J.]]
[[Category: Domaille, P J.]]
[[Category: Handel, T.M.]]
[[Category: Handel, T M.]]
[[Category: chemoattractant cytokine]]
[[Category: chemoattractant cytokine]]
[[Category: high resolution structure]]
[[Category: high resolution structure]]
[[Category: homodimer]]
[[Category: homodimer]]


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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:18:47 2008''

Revision as of 13:18, 21 February 2008

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1don

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SOLUTION STRUCTURE OF THE MONOCYTE CHEMOATTRACTANT PROTEIN-1 DIMER USING HETERONUCLEAR, NMR, 20 STRUCTURES

OverviewOverview

A full high-resolution three-dimensional solution structure of the monocyte chemoattractant protein-1 (MCP-1 or MCAF) homodimer has been determined by heteronuclear multidimensional NMR. MCP-1 is a member of a family of small proteins which play a crucial role in immune surveillance by orchestrating the recruitment of specific leukocytes to areas of immune challenge. The protein was uniformly isotopically enriched with 13C and 15N by expression in Escherichia coli, and complete sequence-specific resonance assignments were obtained by a combination of heteronuclear double- and triple-resonance experiments. The secondary structure was deduced from characteristic patterns of NOEs, 13 C alpha/beta chemical shifts, measurements of 3JHNH alpha scalar couplings, and patterns of slowly exchanging amide protons. Because MCP-1 forms symmetrical homodimers, additional experiments were carried out to unambiguously establish the quaternary contacts. NOEs from these novel experiments were merged with more traditional heteronuclear separated NOE measurements in an iterative strategy to partition the restraints between explicit inter/intrasubunit contacts and a class wherein both were retained as ambiguous. With more than 30 restraints per residue, the three-dimensional structure is well-defined with a backbone rmsd of 0.37 A to the mean over residues 5-69 of the dimer. We compare the structure with those recently reported for the related chemokines MIP-1 beta and RANTES and highlight the differences in terms of receptor specificity and function as well as interpret the known biological activity data of MCP-1 mutants.

DiseaseDisease

Known diseases associated with this structure: Coronary artery disease, modifier of OMIM:[158105], HIV-1, resistance to OMIM:[158105], Mycobacterium tuberculosis, susceptibility to OMIM:[158105], Spina bifida, susceptiblity to OMIM:[158105]

About this StructureAbout this Structure

1DON is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Heteronuclear (1H, 13C, 15N) NMR assignments and solution structure of the monocyte chemoattractant protein-1 (MCP-1) dimer., Handel TM, Domaille PJ, Biochemistry. 1996 May 28;35(21):6569-84. PMID:8639605

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