HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 25, 22930-22940, June 22, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/25/22930    most recent M102300200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zeng, H. Articles by Hawrot, E. Search for Related Content PubMed PubMed Citation Articles by Zeng, H. Articles by Hawrot, E. Social Bookmarking                      What's this?

The Solution Structure of the Complex Formed between -Bungarotoxin and an 18-mer Cognate Peptide Derived from the 1 Subunit of the Nicotinic Acetylcholine Receptor from Torpedo californica^*

Haoyu Zeng^§, Leonard Moise, Marianne A. Grant^¶, and Edward Hawrot

From the  Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown Medical School, Providence, Rhode Island 02912

The region encompassing residues 181-98 on the 1 subunit of the muscle-type nicotinic acetylcholine receptor forms a major determinant for the binding of -neurotoxins. We have prepared an ¹⁵N-enriched 18-amino acid peptide corresponding to the sequence in this region to facilitate structural elucidation by multidimensional NMR. Our aim was to determine the structural basis for the high affinity, stoichiometric complex formed between this cognate peptide and -bungarotoxin, a long -neurotoxin. Resonances in the complex were assigned through heteronuclear and homonuclear NMR experiments, and the resulting interproton distance constraints were used to generate ensemble structures of the complex. Thr⁸, Pro¹⁰, Lys³⁸, Val³⁹, Val⁴⁰, and Pro⁶⁹ in -bungarotoxin and Tyr¹⁸⁹, Tyr¹⁹⁰, Thr¹⁹¹, Cys¹⁹², Asp¹⁹⁵, and Thr¹⁹⁶ in the peptide participate in major intermolecular contacts. A comparison of the free and bound -bungarotoxin structures reveals significant conformational rearrangements in flexible regions of -bungarotoxin, mainly loops I, II, and the C-terminal tail. Furthermore, several of the calculated structures suggest that cation- interactions may be involved in binding. The root mean square deviation of the polypeptide backbone in the complex is 2.07 Å. This structure provides, to date, the highest resolution description of the contacts between a prototypic -neurotoxin and its cognate recognition sequence.

The atomic coordinates and the structure factors (code 1IDG, 1IDH, 1IDI, and 1IDL ) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati