The structure-specific DNA-binding protein HMGB1 (high-mobility group protein B1) which comprises two tandem HMG boxes (A and B) and an acidic C-terminal tail, is acetylated in vivo at Lys2 and Lys11 in the A box. Mutation to alanine of both residues in the isolated A domain, which has a strong preference for pre-bent DNA, abolishes binding to four-way junctions and 88 bp DNA minicircles. The same mutations in full-length HMGB1 also abolish its binding to four-way junctions, and binding to minicircles is substantially impaired. In contrast, when the acidic tail is absent (AB di-domain) there is little effect of the double mutation on four-way junction binding, although binding to minicircles is reduced ∼15-fold. Therefore it appears that in AB the B domain is able to substitute for the non-functional A domain, whereas in full-length HMGB1 the B domain is masked by the acidic tail. In no case does single substitution of Lys2 or Lys11 abolish DNA binding. The double mutation does not significantly perturb the structure of the A domain. We conclude that Lys2 and Lys11 are critical for binding of the isolated A domain and HMGB1 to distorted DNA substrates.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
May 2008
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
April 14 2008
A critical role in structure-specific DNA binding for the acetylatable lysine residues in HMGB1
René Assenberg;
1Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, U.K.
Search for other works by this author on:
Michelle Webb;
1Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, U.K.
Search for other works by this author on:
Edward Connolly;
Edward Connolly
4
1Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, U.K.
Search for other works by this author on:
Katherine Stott;
Katherine Stott
1Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, U.K.
Search for other works by this author on:
Matthew Watson;
Matthew Watson
1Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, U.K.
Search for other works by this author on:
Josie Hobbs;
Josie Hobbs
5
1Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, U.K.
Search for other works by this author on:
Jean O. Thomas
Jean O. Thomas
6
1Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, U.K.
6To whom correspondence should be addressed (email [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
November 28 2007
Revision Received:
February 01 2008
Accepted:
February 01 2008
Accepted Manuscript online:
February 01 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 411 (3): 553–561.
Article history
Received:
November 28 2007
Revision Received:
February 01 2008
Accepted:
February 01 2008
Accepted Manuscript online:
February 01 2008
Citation
René Assenberg, Michelle Webb, Edward Connolly, Katherine Stott, Matthew Watson, Josie Hobbs, Jean O. Thomas; A critical role in structure-specific DNA binding for the acetylatable lysine residues in HMGB1. Biochem J 1 May 2008; 411 (3): 553–561. doi: https://doi.org/10.1042/BJ20071613
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |