Stoll, Raphael and Renner, Christian and Buettner, Reinhard and Voelter, Wolfgang and Bosserhoff, Anja-Katrin and Holak, Tad 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). pp. 510-519. ISSN 0961-8368
Full text not available from this repository.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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MELANOMA-INHIBITORY ACTIVITY; PROLINE-RICH PEPTIDES; MALIGNANT-MELANOMA; PHOTOSYSTEM-I; ROTATIONAL DIFFUSION; CLINICAL RELEVANCE; TYROSINE KINASE; SERUM MARKER; IDENTIFICATION; BINDING; backbone dynamics; binding to SH3 domains |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Aug 2021 11:08 |
| Last Modified: | 24 Aug 2021 11:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39256 |
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