Lymphocyte function-associated antigen-1 (LFA-1) is an integrin protein that transmits information across the plasma membrane through the so-called inside-out and outside-in signaling mechanisms. To investigate these mechanisms, we carried out an NMR analysis of the dynamics of the LFA-1 I-domain, which has enabled us to characterize the motions of this domain on a broad range of timescales. We studied first the internal motions on the nanosecond timescale by spin relaxation measurements and model-free analysis. We then extended this analysis to the millisecond timescale motions by measuring 15N-1H residual dipolar couplings of the backbone amide groups. We analyzed these results in the context of the three major conformational states of the I-domain using their corresponding X-ray crystallographic structures. Our results highlight the importance of the low-frequency motions of the LFA-1 I-domain in the inactive apo-state. We found in particular that ?-helix 7 is in a position in the apo-closed state that cannot be fully described by any of the existing X-ray structures, as it appears to be in dynamic exchange between different conformations. This type of motion seems to represent an inherent property of the LFA-1 I-domain and might be relevant for controlling the access to the allosteric binding pocket, as well as for the downward displacement of ?-helix 7 that is required for the activation of LFA-1.
[NMR paper] NMR characterisation of the conformational fluctuations of the human lymphocyte function associated antigen-1 i domain.
NMR characterisation of the conformational fluctuations of the human lymphocyte function associated antigen-1 i domain.
Related Articles NMR characterisation of the conformational fluctuations of the human lymphocyte function associated antigen-1 i domain.
Protein Sci. 2014 Aug 21;
Authors: Leung HT, Kukic P, Camilloni C, Bemporad F, DeSimone A, Aprile FA, Kumita J, Vendruscolo M
Abstract
Lymphocyte function-associated antigen-1 (LFA-1) is an integrin protein that transmits information across the plasma membrane through the...
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08-26-2014 01:25 PM
NMR characterisation of the conformational fluctuations of the human lymphocyte function associated antigen-1 i domain
NMR characterisation of the conformational fluctuations of the human lymphocyte function associated antigen-1 i domain
Abstract
Lymphocyte function-associated antigen-1 (LFA-1) is an integrin protein that transmits information across the plasma membrane through the so-called ‘inside-out’ and ‘outside-in’ signalling mechanism. To investigate this mechanism, we carried out an NMR analysis of the dynamics of the LFA-1 I-domain, which has enabled us to characterise the motions of this domain on a broad range of timescales. We studied first the internal motions on the nanosecond timescale...
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08-21-2014 06:43 PM
[NMR paper] Characterization of the near native conformational states of the SAM domain of Ste11 protein by NMR spectroscopy.
Characterization of the near native conformational states of the SAM domain of Ste11 protein by NMR spectroscopy.
Related Articles Characterization of the near native conformational states of the SAM domain of Ste11 protein by NMR spectroscopy.
Proteins. 2014 Jul 26;
Authors: Gupta S, Bhattacharjya S
Abstract
The sterile alpha motif or SAM domain is one of the most frequently present protein interaction modules with diverse functional attributions. SAM domain of the Ste11 protein of budding yeast plays important roles in...
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07-30-2014 10:22 AM
[NMR paper] Expression and structural characterization of anti-T-antigen single chain antibodies (scFvs) and analysis of their binding to T-antigen by surface plasmon resonance and NMR spectroscopy.
Expression and structural characterization of anti-T-antigen single chain antibodies (scFvs) and analysis of their binding to T-antigen by surface plasmon resonance and NMR spectroscopy.
Expression and structural characterization of anti-T-antigen single chain antibodies (scFvs) and analysis of their binding to T-antigen by surface plasmon resonance and NMR spectroscopy.
J Biochem. 2013 Oct 4;
Authors: Yuasa N, Koyama T, Subedi GP, Yamaguchi Y, Matsushita M, Fujita-Yamaguchi Y
Abstract
T-antigen (Gal?1-3GalNAc?-1-Ser/Thr), also known as...
[NMR paper] Metal-dependent conformational changes in a recombinant vWF-A domain from human facto
Metal-dependent conformational changes in a recombinant vWF-A domain from human factor B: a solution study by circular dichroism, fourier transform infrared and (1)H NMR spectroscopy.
Related Articles Metal-dependent conformational changes in a recombinant vWF-A domain from human factor B: a solution study by circular dichroism, fourier transform infrared and (1)H NMR spectroscopy.
J Mol Biol. 2000 Apr 21;298(1):135-47
Authors: Hinshelwood J, Perkins SJ
Factor B is a key component of the alternative pathway of complement and is cleaved by...
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11-18-2010 09:15 PM
[NMR paper] NMR solution structure of the inserted domain of human leukocyte function associated
NMR solution structure of the inserted domain of human leukocyte function associated antigen-1.
Related Articles NMR solution structure of the inserted domain of human leukocyte function associated antigen-1.
J Mol Biol. 2000 Feb 4;295(5):1251-64
Authors: Legge GB, Kriwacki RW, Chung J, Hommel U, Ramage P, Case DA, Dyson HJ, Wright PE
The interaction between the leukocyte function-associated antigen-1 (LFA-1) and the intercellular adhesion molecule is thought to be mediated primarily via the inserted domain (I-domain) in the alpha-subunit. The...
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[NMR paper] Contributions to conformational entropy arising from bond vector fluctuations measure
Contributions to conformational entropy arising from bond vector fluctuations measured from NMR-derived order parameters: application to protein folding.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles Contributions to conformational entropy arising from bond vector fluctuations measured from NMR-derived order parameters: application to protein folding.
J Mol Biol. 1996 Oct 25;263(2):369-82
Authors: Yang D, Kay LE
The relation between order parameters derived from NMR...
NMR characterization of the conformational fluctuations of the human lymphocyte function-associated antigen-1 I-domain
Linear Mode
