1l5c: Difference between revisions

Revision as of 14:41, 21 February 2008

Solution Structure of the Monomeric Form of a Mutant Unliganded Bovine Neurophysin, 20 Structures

OverviewOverview

Determination of the structure of the unliganded monomeric state of neurophysin is central to an understanding of the allosteric relationship between neurophysin peptide-binding and dimerization. We examined this state by NMR, using the weakly dimerizing H80E mutant of bovine neurophysin-I. The derived structure, to which more than one conformer appeared to contribute, was compared with the crystal structure of the unliganded des 1-6 bovine neurophysin-II dimer. Significant conformational differences between the two proteins were evident in the orientation of the 3,10 helix, in the 50-58 loop, in beta-turns, and in specific intrachain contacts between amino- and carboxyl domains. However, both had similar secondary structures, in independent confirmation of earlier circular dichroism studies. Previously suggested interactions between the amino terminus and the 50-58 loop in the monomer were also confirmed. Comparison of the observed differences between the two proteins with demonstrated effects of dimerization on the NMR spectrum of bovine neurophysin-I, and preliminary investigation of the effects of dimerization on H80E spectra, allowed tentative distinction between the contributions of sequence and self-association differences to the difference in conformation. Regions altered by dimerization encompass most binding site residues, providing a potential explanation of differences in binding affinity between the unliganded monomeric and dimeric states. Differences between monomer and dimer states in turns, interdomain contacts, and within the interdomain segment of the 50-58 loop suggest that the effects of dimerization on intrasubunit conformation reflect the need to adjust the relative positions of the interface segments of the two domains for optimal interaction with the adjacent subunit and/or reflect the dual role of some residues as participants both at the interface and in interdomain contacts.

About this StructureAbout this Structure

1L5C is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.

ReferenceReference

NMR analysis of the monomeric form of a mutant unliganded bovine neurophysin: comparison with the crystal structure of a neurophysin dimer., Nguyen TL, Breslow E, Biochemistry. 2002 May 7;41(18):5920-30. PMID:11980496

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-[[Image:1l5c.jpg|left|200px]]<br /><applet load="1l5c" size="450" color="white" frame="true" align="right" spinBox="true"
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 caption="1l5c" />
 '''Solution Structure of the Monomeric Form of a Mutant Unliganded Bovine Neurophysin, 20 Structures'''<br />
 ==Overview==
-Determination of the structure of the unliganded monomeric state of, neurophysin is central to an understanding of the allosteric relationship, between neurophysin peptide-binding and dimerization. We examined this, state by NMR, using the weakly dimerizing H80E mutant of bovine, neurophysin-I. The derived structure, to which more than one conformer, appeared to contribute, was compared with the crystal structure of the, unliganded des 1-6 bovine neurophysin-II dimer. Significant conformational, differences between the two proteins were evident in the orientation of, the 3,10 helix, in the 50-58 loop, in beta-turns, and in specific, intrachain contacts between amino- and carboxyl domains. However, both had, similar secondary structures, in independent confirmation of earlier, circular dichroism studies. Previously suggested interactions between the, amino terminus and the 50-58 loop in the monomer were also confirmed., Comparison of the observed differences between the two proteins with, demonstrated effects of dimerization on the NMR spectrum of bovine, neurophysin-I, and preliminary investigation of the effects of, dimerization on H80E spectra, allowed tentative distinction between the, contributions of sequence and self-association differences to the, difference in conformation. Regions altered by dimerization encompass most, binding site residues, providing a potential explanation of differences in, binding affinity between the unliganded monomeric and dimeric states., Differences between monomer and dimer states in turns, interdomain, contacts, and within the interdomain segment of the 50-58 loop suggest, that the effects of dimerization on intrasubunit conformation reflect the, need to adjust the relative positions of the interface segments of the two, domains for optimal interaction with the adjacent subunit and/or reflect, the dual role of some residues as participants both at the interface and, in interdomain contacts.
+Determination of the structure of the unliganded monomeric state of neurophysin is central to an understanding of the allosteric relationship between neurophysin peptide-binding and dimerization. We examined this state by NMR, using the weakly dimerizing H80E mutant of bovine neurophysin-I. The derived structure, to which more than one conformer appeared to contribute, was compared with the crystal structure of the unliganded des 1-6 bovine neurophysin-II dimer. Significant conformational differences between the two proteins were evident in the orientation of the 3,10 helix, in the 50-58 loop, in beta-turns, and in specific intrachain contacts between amino- and carboxyl domains. However, both had similar secondary structures, in independent confirmation of earlier circular dichroism studies. Previously suggested interactions between the amino terminus and the 50-58 loop in the monomer were also confirmed. Comparison of the observed differences between the two proteins with demonstrated effects of dimerization on the NMR spectrum of bovine neurophysin-I, and preliminary investigation of the effects of dimerization on H80E spectra, allowed tentative distinction between the contributions of sequence and self-association differences to the difference in conformation. Regions altered by dimerization encompass most binding site residues, providing a potential explanation of differences in binding affinity between the unliganded monomeric and dimeric states. Differences between monomer and dimer states in turns, interdomain contacts, and within the interdomain segment of the 50-58 loop suggest that the effects of dimerization on intrasubunit conformation reflect the need to adjust the relative positions of the interface segments of the two domains for optimal interaction with the adjacent subunit and/or reflect the dual role of some residues as participants both at the interface and in interdomain contacts.
 ==About this Structure==
-L5C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1L5C OCA].
+L5C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L5C OCA].
 ==Reference==
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 [[Category: Single protein]]
 [[Category: Breslow, E.]]
-[[Category: Nguyen, T.L.]]
+[[Category: Nguyen, T L.]]
 [[Category: nmr analysis neurophysin monomer]]
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+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:41:29 2008''