Determinants of protein-protein recognition by four helix bundles: changing the dimerization specificity of Tet repressor

The EMBO Journal
D SchnappingerWolfgang Hillen

Abstract

Homo- and heterodimerization is essential for the activity of many proteins, particularly transcription factors. One widely distributed structural motif for protein recognition is the four helix bundle. To understand the molecular details determining specificity of subunit recognition in a dimer formed by a four helix bundle, we investigated Tet repressor (TetR) sequence variants TetR(B) and TetR(D), which do not form heterodimers. We used molecular modeling to identify residues with the potential to determine recognition of subunits. Directed mutagenesis of these residues in TetR(B) by the TetR(D) sequence resulted in chimeric TetR(B/D) repressors with new subunit recognition specificities. The single LS192 exchange in TetR(B/D)192 in the center of the helix bundle leads to a relaxed specificity since this variant dimerizes with TetR(B) and (D). To construct a variant with a new specificity it was not sufficient to mutate the contacting residue, F197, in the other subunit. Instead, it was necessary to exchange two more residues in the vicinity of F197 and S192. The resulting TetR(B/D)188, 192,193,197 forms dimers with TetR(D) but not with TetR(B), indicating that four amino acid exchanges are sufficient to change subunit recog...Continue Reading

References

Jan 1, 1992·Annual Review of Biochemistry·C O Pabo, R T Sauer
May 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·T Hai, T Curran
Dec 15, 1988·Nature·T Kouzarides, E Ziff
Nov 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·M H Yu, J King
Dec 1, 1994·Protein Science : a Publication of the Protein Society·K E Neet, D E Timm
Dec 23, 1994·Science·A Sancar
Jan 1, 1994·Annual Review of Microbiology·W Hillen, C Berens
Jun 21, 1994·Proceedings of the National Academy of Sciences of the United States of America·H L HsuR Baer
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·J A Wells
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·S Jones, J M Thornton
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·D R Davies, G H Cohen
Oct 1, 1996·Trends in Biochemical Sciences·A Lupas
Mar 14, 1997·The Journal of Biological Chemistry·C BerensW Hillen
Apr 10, 1997·Nature·M Ptashne, A Gann

❮ Previous
Next ❯

Citations

May 22, 2003·Journal of Molecular Biology·Oliver ScholzWolfgang Hillen
Aug 11, 2006·Nucleic Acids Research·Annette KamionkaWolfgang Hillen
Feb 3, 2005·Nucleic Acids Research·Sabine EhrtDirk Schnappinger
May 22, 2004·European Journal of Biochemistry·Peter SchubertWolfgang Hillen
Feb 3, 2009·Applied and Environmental Microbiology·Inka SastallaStephen H Leppla
Jun 19, 2004·Journal of Bacteriology·Annette KamionkaWolfgang Hillen
Nov 29, 2002·Microbiology and Molecular Biology Reviews : MMBR·Steve GrkovicRonald A Skurray
Jun 3, 2000·Annual Review of Pharmacology and Toxicology·C R OzawaH M Blau
Jun 1, 2005·Journal of Molecular Microbiology and Biotechnology·Ralph BertramWolfgang Hillen
Feb 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·H M Blau, F M Rossi
Sep 24, 2013·Applied and Environmental Microbiology·Aleksandra W DebowskiMohammed Benghezal
Sep 8, 2010·Journal of Molecular Biology·Martin T StiebritzYves A Muller
Jul 17, 2004·Molecular Microbiology·Oliver ScholzWolfgang Hillen
Jan 1, 2008·Microbial Biotechnology·Ralph Bertram, Wolfgang Hillen
Oct 28, 2011·Biotechnology Journal·Joseph A GredellPatrick C Cirino
Jul 16, 2010·Molecular Systems Biology·Jian ZhanHaiyan Liu
Dec 20, 2011·Journal of Molecular Biology·Dagmar GoekeWolfgang Hillen
Jul 28, 2006·Chembiochem : a European Journal of Chemical Biology·Christian BerensPeter Gmeiner
Jun 17, 2006·The Journal of Gene Medicine·Christel KruegerChristian Berens
May 5, 2005·The Journal of Biological Chemistry·Marcus KlotzscheWolfgang Hillen
May 16, 2019·BMC Bioinformatics·Najaf A Shah, Casim A Sarkar
Jun 27, 1998·Journal of Molecular Biology·P OrthW Hinrichs
Jun 20, 2021·Journal of Molecular Biology·Julia DietlerAndreas Möglich
Jul 21, 2004·Biochemistry·Eva-Maria HensslerWolfgang Hillen
Oct 30, 2021·Microbial Biotechnology·Ralph BertramChristopher F Schuster

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.