Role of conserved Salt bridges in homeodomain stability and DNA binding

  1. Torrado, M. 1
  2. Revuelta, J. 1
  3. Gonzalez, C. 2
  4. Corzana, F. 3
  5. Bastida, A. 1
  6. Asensio, J.L. 1
  1. 1 Instituto de Química Orgánica General
    info

    Instituto de Química Orgánica General

    Madrid, España

    ROR https://ror.org/05e0q7s59

  2. 2 Instituto de Química Física Rocasolano
    info

    Instituto de Química Física Rocasolano

    Madrid, España

    ROR https://ror.org/03xk60j79

  3. 3 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

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Revista:
Journal of Biological Chemistry (Print)

ISSN: 0021-9258

Any de publicació: 2009

Volum: 284

Número: 35

Pàgines: 23765-23779

Tipus: Article

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DOI: 10.1074/JBC.M109.012054 PMID: 19561080 SCOPUS: 2-s2.0-69949155029 WoS: WOS:000269180000061 GOOGLE SCHOLAR

Altres publicacions en: Journal of Biological Chemistry (Print)

Repositori institucional: lock_openAccés obert Editor

Objectius de Desenvolupament Sostenible

Resum

The sequence information available for homeodomains reveals that salt bridges connecting pairs 19/30, 31/42, and 17/52 are frequent, whereas aliphatic residues at these sites are rare and mainly restricted to proteins from homeotherms. We have analyzed the influence of salt and hydrophobic bridges at these sites on the stability and DNA binding properties of human Hesx-1 homeodomain. Regarding the protein stability, our analysis shows that hydrophobic side chains are clearly preferred at positions 19/30 and 31/42. This stabilizing influence results from the more favorable packing of the aliphatic side chains with the protein core, as illustrated by the three-dimensional solution structure of a thermostable variant, herein reported. In contrast only polar side chains seem to be tolerated at positions 17/52. Interestingly, despite the significant influence of pairs 19/30 and 31/42 on the stability of the homeodomain, their effect on DNA binding ranges from modest to negligible. The observed lack of correlation between binding strength and conformational stability in the analyzed variants suggests that salt/ hydrophobic bridges at these specific positions might have been employed by evolution to independently modulate both properties. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.