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  Backbone dynamics of the human MIA protein studied by N-15 NMR relaxation: Implications for extended interactions of SH3 domains

Stoll, R., Renner, C., Buettner, R., Voelter, W., Bosserhoff, A. K., & Holak, T. A. (2003). Backbone dynamics of the human MIA protein studied by N-15 NMR relaxation: Implications for extended interactions of SH3 domains. Protein Science, 12(3), 510-519.

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Genre: Journal Article
Alternative Title : Protein Sci.

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 Creators:
Stoll, R., Author
Renner, C.1, Author              
Buettner, R., Author
Voelter, W., Author
Bosserhoff, A. K.2, Author              
Holak, T. A.3, Author              
Affiliations:
1Moroder, Luis / Bioorganic Chemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565160              
2External Organizations, ou_persistent22              
3Holak, Tad / NMR Spectroscopy, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565154              

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Free keywords: backbone dynamics; binding to SH3 domains
 Abstract: The melanoma inhibitory activity (MIA) protein is a clinically valuable marker in patients with malignant melanoma as enhanced values diagnose metastatic melanoma stages III and IV. Here, we report the backbone dynamics of human MIA studied by N-15 NMR relaxation experiments. The folded core of human MIA is found to be rigid, but several loops connecting beta-sheets, such as the RT-loop for example, display increased mobility on picosecond to nanosecond time scales. One of the most important dynamic features is the pronounced flexibility of the distal loop, comprising residues Asp 68 to Ala 75, where motions on time scales up to milliseconds occur. Further, significant exchange contributions are observed for residues of the canonical binding site of SH3 domains including the RT-loop, the n-Src loop, for the loop comprising residues 13 to 19, which we refer to as the "disulfide loop", in pan for the distal loop, and the carboxyl terminus of human MIA. The functional importance of this dynamic behavior is discussed with respect to the biological activity of several point mutations of human MIA. The results of this study suggest that the MIA protein and the recently identified highly homologous fibrocyte-derived protein (FDP)/MIA-like (MIAL) constitute a new family of secreted proteins that adopt an SH3 domain-like fold in solution with expanded ligand interactions.

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Language(s): eng - English
 Dates: 2003-03
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 41342
ISI: 000181354100011
 Degree: -

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Title: Protein Science
  Alternative Title : Protein Sci.
Source Genre: Journal
 Creator(s):
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Publ. Info: -
Pages: - Volume / Issue: 12 (3) Sequence Number: - Start / End Page: 510 - 519 Identifier: ISSN: 0961-8368