Solution NMR structure of S100B bound to the high-affinity target peptide TRTK-12.

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TitleSolution NMR structure of S100B bound to the high-affinity target peptide TRTK-12.
Publication TypeJournal Article
Year of Publication2002
AuthorsInman, KG, Yang, R, Rustandi, RR, Miller, KE, Baldisseri, DM, Weber, DJ
JournalJ Mol Biol
Volume324
Issue5
Pagination1003-14
Date Published2002 Dec 13
ISSN0022-2836
KeywordsAmino Acid Sequence, Calcium, CapZ Actin Capping Protein, Consensus Sequence, EF Hand Motifs, Magnetic Resonance Spectroscopy, Microfilament Proteins, Models, Molecular, Muscle Proteins, Nerve Growth Factors, Nuclear Magnetic Resonance, Biomolecular, Peptides, Protein Binding, Protein Structure, Secondary, Protein Subunits, S100 Proteins, Solutions, Substrate Specificity, Tumor Suppressor Protein p53
Abstract

The solution NMR structure is reported for Ca(2+)-loaded S100B bound to a 12-residue peptide, TRTK-12, from the actin capping protein CapZ (alpha1 or alpha2 subunit, residues 265-276: TRTKIDWNKILS). This peptide was discovered by Dimlich and co-workers by screening a bacteriophage random peptide display library, and it matches exactly the consensus S100B binding sequence ((K/R)(L/I)XWXXIL). As with other S100B target proteins, a calcium-dependent conformational change in S100B is required for TRTK-12 binding. The TRTK-12 peptide is an amphipathic helix (residues W7 to S12) in the S100B-TRTK complex, and helix 4 of S100B is extended by three or four residues upon peptide binding. However, helical TRTK-12 in the S100B-peptide complex is uniquely oriented when compared to the three-dimensional structures of other S100-peptide complexes. The three-dimensional structure of the S100B-TRTK peptide complex illustrates that residues in the S100B binding consensus sequence (K4, I5, W7, I10, L11) are all involved in the S100B-peptide interface, which can explain its orientation in the S100B binding pocket and its relatively high binding affinity. A comparison of the S100B-TRTK peptide structure to the structures of apo- and Ca(2+)-bound S100B illustrates that the binding site of TRTK-12 is buried in apo-S100B, but is exposed in Ca(2+)-bound S100B as necessary to bind the TRTK-12 peptide.

Alternate JournalJ. Mol. Biol.
PubMed ID12470955
Grant ListGM58888 / GM / NIGMS NIH HHS / United States