1mq1

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==Overview==
==Overview==
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The Alzheimer-linked neural protein S100B is a signaling molecule shown to, control the assembly of intermediate filament proteins in a, calcium-sensitive manner. Upon binding calcium, a conformational change, occurs in S100B exposing a hydrophobic surface for target protein, interactions. The synthetic peptide TRTK-12 (TRTKIDWNKILS), derived from, random bacteriophage library screening, bears sequence similarity to, several intermediate filament proteins and has the highest, calcium-dependent affinity of any target molecule for S100B to date (K(d), <1 microm). In this work, the three-dimensional structure of the, Ca(2+)-S100B-TRTK-12 complex has been determined by NMR spectroscopy. The, structure reveals an extended, contiguous hydrophobic surface is formed on, Ca(2+)-S100B for target interaction. The TRTK-12 peptide adopts a coiled, structure that fits into a portion of this surface, anchored at Trp(7), and interacts with multiple hydrophobic contacts in helices III and IV of, Ca(2+)-S100B. This interaction is strikingly different from the, alpha-helical structures found for other S100 target peptides. By using, the TRTK-12 interaction as a guide, in combination with other available, S100 target structures, a recognition site on helix I is identified that, may act in concert with the TRTK-12-binding site from helices III and IV., This would provide a larger, more complex site to interact with, full-length target proteins and would account for the promiscuity observed, for S100B target protein interactions.
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The Alzheimer-linked neural protein S100B is a signaling molecule shown to control the assembly of intermediate filament proteins in a calcium-sensitive manner. Upon binding calcium, a conformational change occurs in S100B exposing a hydrophobic surface for target protein interactions. The synthetic peptide TRTK-12 (TRTKIDWNKILS), derived from random bacteriophage library screening, bears sequence similarity to several intermediate filament proteins and has the highest calcium-dependent affinity of any target molecule for S100B to date (K(d) <1 microm). In this work, the three-dimensional structure of the Ca(2+)-S100B-TRTK-12 complex has been determined by NMR spectroscopy. The structure reveals an extended, contiguous hydrophobic surface is formed on Ca(2+)-S100B for target interaction. The TRTK-12 peptide adopts a coiled structure that fits into a portion of this surface, anchored at Trp(7), and interacts with multiple hydrophobic contacts in helices III and IV of Ca(2+)-S100B. This interaction is strikingly different from the alpha-helical structures found for other S100 target peptides. By using the TRTK-12 interaction as a guide, in combination with other available S100 target structures, a recognition site on helix I is identified that may act in concert with the TRTK-12-binding site from helices III and IV. This would provide a larger, more complex site to interact with full-length target proteins and would account for the promiscuity observed for S100B target protein interactions.
==About this Structure==
==About this Structure==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: McClintock, K.A.]]
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[[Category: McClintock, K A.]]
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[[Category: Shaw, G.S.]]
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[[Category: Shaw, G S.]]
[[Category: ef-hand]]
[[Category: ef-hand]]
[[Category: protein-peptide complex]]
[[Category: protein-peptide complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:25:10 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:57:50 2008''

Revision as of 11:57, 21 February 2008


1mq1

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Ca2+-S100B-TRTK-12 complex

Overview

The Alzheimer-linked neural protein S100B is a signaling molecule shown to control the assembly of intermediate filament proteins in a calcium-sensitive manner. Upon binding calcium, a conformational change occurs in S100B exposing a hydrophobic surface for target protein interactions. The synthetic peptide TRTK-12 (TRTKIDWNKILS), derived from random bacteriophage library screening, bears sequence similarity to several intermediate filament proteins and has the highest calcium-dependent affinity of any target molecule for S100B to date (K(d) <1 microm). In this work, the three-dimensional structure of the Ca(2+)-S100B-TRTK-12 complex has been determined by NMR spectroscopy. The structure reveals an extended, contiguous hydrophobic surface is formed on Ca(2+)-S100B for target interaction. The TRTK-12 peptide adopts a coiled structure that fits into a portion of this surface, anchored at Trp(7), and interacts with multiple hydrophobic contacts in helices III and IV of Ca(2+)-S100B. This interaction is strikingly different from the alpha-helical structures found for other S100 target peptides. By using the TRTK-12 interaction as a guide, in combination with other available S100 target structures, a recognition site on helix I is identified that may act in concert with the TRTK-12-binding site from helices III and IV. This would provide a larger, more complex site to interact with full-length target proteins and would account for the promiscuity observed for S100B target protein interactions.

About this Structure

1MQ1 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

A novel S100 target conformation is revealed by the solution structure of the Ca2+-S100B-TRTK-12 complex., McClintock KA, Shaw GS, J Biol Chem. 2003 Feb 21;278(8):6251-7. Epub 2002 Dec 11. PMID:12480931

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