Odorants are transmitted by small hydrophobic molecules that cross the aqueous sensillar lymph surrounding the dendrites of the olfactory neurons to stimulate the olfactory receptors. In insects, the transport of pheromones, which are a special class of odorants, is mediated by pheromone-binding proteins (PBPs), which occur at high concentrations in the sensillar lymph. The PBP from the silk moth Bombyx mori (BmPBP) undergoes a pH-dependent conformational transition between the forms BmPBP(A) present at pH 4.5 and BmPBP(B) present at pH 6.5. Here, we describe the NMR structure of BmPBP(A), which consists of a tightly packed arrangement of seven alpha-helices linked by well defined peptide segments and knitted together by three disulfide bridges. A scaffold of four alpha-helices that forms the ligand binding site in the crystal structure of a BmPBP-pheromone complex is preserved in BmPBP(A). The C-terminal dodecapeptide segment, which is in an extended conformation and located on the protein surface in the pheromone complex, forms a regular helix, alpha(7), which is located in the pheromone-binding site in the core of the unliganded BmPBP(A). Because investigations by others indicate that the pH value near the membrane surface is reduced with respect to the bulk sensillar lymph, the pH-dependent conformational transition of BmPBP suggests a novel physiological mechanism of intramolecular regulation of protein function, with the formation of alpha(7) triggering the release of the pheromone from BmPBP to the membrane-standing receptor.
NMR reveals novel mechanisms of protein activity regulation.
NMR reveals novel mechanisms of protein activity regulation.
NMR reveals novel mechanisms of protein activity regulation.
Protein Sci. 2011 Mar 14;
Authors: Kalodimos CG
NMR spectroscopy is one of the most powerful tools for the characterization of biomolecular systems. A unique aspect of NMR is its capacity to provide an integrated insight into both the structure and intrinsic dynamics of biomolecules. In addition, NMR can provide site-resolved information about the conformation entropy of binding, as well as about energetically excited...
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03-16-2011 04:15 PM
NMR analysis of the αIIbβ3 cytoplasmic interaction suggests a mechanism for integrin regulation [Biochemistry]
NMR analysis of the αIIbβ3 cytoplasmic interaction suggests a mechanism for integrin regulation
Metcalf, D. G., Moore, D. T., Wu, Y., Kielec, J. M., Molnar, K., Valentine, K. G., Wand, A. J., Bennett, J. S., DeGrado, W. F....
Date: 2010-12-28
The integrin ?IIb?3 is a transmembrane (TM) heterodimeric adhesion receptor that exists in equilibrium between resting and active ligand binding conformations. In resting ?IIb?3, the TM and cytoplasmic domains of ?IIb and ?3 form a heterodimer that constrains ?IIb?3 in its resting conformation. To study the structure and dynamics of...
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01-03-2011 10:48 PM
NMR analysis of the {alpha}IIb{beta}3 cytoplasmic interaction suggests a mechanism for integrin regulation [Biochemistry]
NMR analysis of the {alpha}IIb{beta}3 cytoplasmic interaction suggests a mechanism for integrin regulation
Metcalf, D. G., Moore, D. T., Wu, Y., Kielec, J. M., Molnar, K., Valentine, K. G., Wand, A. J., Bennett, J. S., DeGrado, W. F....
Date: 2010-12-28
The integrin IIbβ3 is a transmembrane (TM) heterodimeric adhesion receptor that exists in equilibrium between resting and active ligand binding conformations. In resting IIbβ3, the TM and cytoplasmic domains of IIb and β3 form a heterodimer that constrains IIbβ3 in its resting conformation. To study the structure...
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12-29-2010 06:01 AM
NMR analysis of the {alpha}IIb{beta}3 cytoplasmic interaction suggests a mechanism for integrin regulation.
NMR analysis of the {alpha}IIb{beta}3 cytoplasmic interaction suggests a mechanism for integrin regulation.
NMR analysis of the {alpha}IIb{beta}3 cytoplasmic interaction suggests a mechanism for integrin regulation.
Proc Natl Acad Sci U S A. 2010 Dec 14;
Authors: Metcalf DG, Moore DT, Wu Y, Kielec JM, Molnar K, Valentine KG, Wand AJ, Bennett JS, Degrado WF
The integrin ?IIb?3 is a transmembrane (TM) heterodimeric adhesion receptor that exists in equilibrium between resting and active ligand binding conformations. In resting ?IIb?3, the TM and...
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12-16-2010 09:21 PM
[NMR paper] NMR structure of the unliganded Bombyx mori pheromone-binding protein at physiologica
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FEBS Lett. 2002 Nov 6;531(2):314-8
Authors: Lee D, Damberger FF, Peng G, Horst R, Güntert P, Nikonova L, Leal WS, Wüthrich K
The nuclear magnetic resonance structure of the unliganded pheromone-binding protein (PBP) from Bombyx mori at pH above 6.5, BmPBP(B), consists of seven helices with residues 3-8, 16-22, 29-32, 46-59, 70-79, 84-100, and...
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11-24-2010 08:58 PM
[NMR paper] Novel mechanism of regulation of the non-receptor protein tyrosine kinase Csk: insigh
Novel mechanism of regulation of the non-receptor protein tyrosine kinase Csk: insights from NMR mapping studies and site-directed mutagenesis.
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J Mol Biol. 2001 Nov 16;314(1):129-38
Authors: Shekhtman A, Ghose R, Wang D, Cole PA, Cowburn D
Csk (C-terminal Src kinase), a protein tyrosine kinase, consisting of the Src homology 2 and 3 (SH2 and SH3) domains and a catalytic domain,...
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11-19-2010 08:44 PM
[NMR paper] NMR structure of free RGS4 reveals an induced conformational change upon binding Galp
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Biochemistry. 2000 Jun 20;39(24):7063-73
Authors: Moy FJ, Chanda PK, Cockett MI, Edris W, Jones PG, Mason K, Semus S, Powers R
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