High Resolution NMR Solution Structure of the Leucine Zipper Domain of the c-Jun Homodimer

doi:10.1074/jbc.271.23.13663

High Resolution NMR Solution Structure of the Leucine Zipper Domain of the c-Jun Homodimer*

From the ^‡ Department of Biochemistry, University of Sydney, Sydney, New South Wales 2006, Australia and
^§ EMBL, Heidelberg D-69012, Federal Republic of Germany

^¶ To whom correspondence should be addressed:
Dept. of Biochemistry, Bldg. GO8, University of Sydney, Sydney, New South Wales 2006, Australia.
Tel.: 61-2-351-3902; Fax: 61-2-351-4726; E-mail: G. King{at}biochem.usyd.edu.au

Abstract

The solution structure of the c-Jun leucine zipper domain has been determined to high resolution using a new calculation protocol designed to handle highly ambiguous sets of interproton distance restraints. The domain comprises a coiled coil of parallel α-helices in which most of the hydrophobic residues are buried at the highly symmetrical dimer interface; this interface extends over 10 helical turns and is the most elongated protein domain solved to date using NMR methods. The backbone fold is very similar to that seen in crystal structures of the GCN4 and Jun-Fos leucine zippers; however, in contrast with these crystal structures, the Jun leucine zipper dimer appears to be devoid of favorable intermolecular electrostatic interactions. A polar asparagine residue, located at the dimer interface, forms the sole point of asymmetry in the structure; furthermore, the side chain of this residue is disordered due to motional averaging. This residue, which is highly conserved in the leucine zipper family of transcription factors, provides a destabilizing influence that is likely to facilitate the rapid exchange of zipper strands in vivo.

Footnotes

↵* This work was supported by grants from the Australian National Health and Medical Research Council (to G. F. K. and A. S. W.), by a C. J. Martin fellowship (to S. I. O'D.), and by a grant from the University of Sydney Cancer Research Fund (to A. S. W. and G. F. K.). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

bZIP

basic domain leucine zipper

rJunLZ

recombinant JunLZ

NOE

nuclear Overhauser effect

MFP

mean force potential

r.m.s.

root mean square

GCN4-LZ

GCN4 leucine zipper

bHLH-LZ

basic domain helix-loop-helix leucine zipper.
↵² The X-PLOR calculation protocol is freely available from http://www.nmr.embl-heidelberg.de/nilges/
- Received January 4, 1996.
- Revision received March 23, 1996.