Source:http://linkedlifedata.com/resource/pubmed/id/15683231
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2005-2-1
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pubmed:abstractText |
The recently cloned colon carcinoma kinase 4 (CCK4) oncogene contains an evolutionarily conserved GxxxG motif in its single transmembrane domain (TMD). It has previously been suggested that this pairwise glycine motif may provide a strong driving force for transmembrane helix-helix interactions. Since CCK4 is thought to represent a new member of the receptor tyrosine kinase family, interactions between the TMDs may be important in receptor self-association and activation of signal transduction pathways. To determine whether this conserved CCK4 TMD can drive protein-protein interactions, we have carried out a thermodynamic study using the TMD expressed as a Staphylococcal nuclease (SN) fusion protein. Similar SN-TMD fusion proteins have been used to determine the sequence specificity and thermodynamics of transmembrane helix-helix interactions in a number of membrane proteins, including glycophorin A. Using sedimentation equilibrium in C14 betaine micelles, we discovered that the CCK4 TMD is unable to drive strong protein-protein interactions. At high protein/detergent ratios, the SN-CCK4 fusion protein will dimerize, but a stochastic model for protein association in micelles can explain the observed dimer population. For low-affinity interactions such as the one studied here, an understanding of this discrete stochastic distribution of membrane proteins in micelles is important for distinguishing between preferential and random self-interactions, which can both influence the oligomeric population. The lack of a thermodynamically meaningful self-association propensity for the CCK4 TMDs demonstrates that a GxxxG motif is not sufficient to drive transmembrane helix-helix interactions.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PTK7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1464-70
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pubmed:dateRevised |
2011-9-22
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pubmed:meshHeading |
pubmed-meshheading:15683231-Amino Acid Motifs,
pubmed-meshheading:15683231-Amino Acid Sequence,
pubmed-meshheading:15683231-Cell Adhesion Molecules,
pubmed-meshheading:15683231-Cloning, Molecular,
pubmed-meshheading:15683231-Humans,
pubmed-meshheading:15683231-Membrane Proteins,
pubmed-meshheading:15683231-Molecular Sequence Data,
pubmed-meshheading:15683231-Peptide Fragments,
pubmed-meshheading:15683231-Protein Structure, Tertiary,
pubmed-meshheading:15683231-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:15683231-Recombinant Fusion Proteins,
pubmed-meshheading:15683231-Thermodynamics,
pubmed-meshheading:15683231-Ultracentrifugation
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pubmed:year |
2005
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pubmed:articleTitle |
The GxxxG-containing transmembrane domain of the CCK4 oncogene does not encode preferential self-interactions.
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pubmed:affiliation |
T. C. Jenkins Department of Biophysics, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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