Specificity in protein-protein recognition: conserved Im9 residues are the major determinants of stability in the colicin E9 DNase-Im9 complex

Biochemistry
R WallisC Kleanthous

Abstract

The endonuclease group of E colicins are a family of bacterial toxins whose cytotoxic activity in a producing host is inactivated by a specific immunity protein. The DNase of colicin E9 can be bound and inhibited by both cognate and noncognate immunity proteins, the dissociation constants for which span a range of 12-orders of magnitude. DNase binding specificity of the immunity proteins is governed primarily by helix II, the sequence of which is variable in this family of proteins. Heteronuclear NMR experiments have identified helix III along with helix II as the likely DNase binding site, although other regions of Im9 also showed perturbations on binding the E9 DNase. In the present work, we have used the NMR experiments as a guide for alanine scanning mutagenesis of Im9. Our data show that helices II and III of Im9 are indeed the DNase binding site and in addition quantitate the relative binding energy associated with each helix. We find that the conserved residues of helix III make the largest relative contribution toward E9 DNase binding. In conjunction with previous studies, the data suggest that specificity in the colicin-immunity system is governed by a dual recognition mechanism in which highly stabilizing interactions...Continue Reading

References

Mar 1, 1992·European Journal of Biochemistry·W Bode, R Huber
Mar 20, 1992·Journal of Molecular Biology·J Foote, G Winter
Jul 15, 1992·European Journal of Biochemistry·R WallisC Kleanthous
Jan 1, 1990·Annual Review of Biochemistry·D R DaviesS Sheriff
Sep 2, 1988·Science·R Schleif
Dec 5, 1993·Journal of Molecular Biology·B C Cunningham, J A Wells
Jan 20, 1995·Science·T Clackson, J A Wells
Jul 13, 1993·Biochemistry·R F Kelley, M P O'Connell
Jan 1, 1995·Proteins·J Janin
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·D R Davies, G H Cohen
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·K F ChakH S Yuan
Aug 2, 1996·Journal of Molecular Biology·C Garinot-SchneiderR James
Jul 1, 1996·Microbiology·R JamesG R Moore

❮ Previous
Next ❯

Citations

Oct 9, 2001·Trends in Biochemical Sciences·C Kleanthous, D Walker
Nov 17, 2011·Quarterly Reviews of Biophysics·Grigorios PapadakosColin Kleanthous
Sep 15, 2009·Nature Structural & Molecular Biology·Kalia Bernath LevinDan S Tawfik
May 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Nicola A G MeenanColin Kleanthous
Mar 12, 2011·Protein Engineering, Design & Selection : PEDS·Stuart KnowlingSheena E Radford
May 4, 2000·Protein Science : a Publication of the Protein Society·S B WhittakerG R Moore
Oct 25, 2000·Protein Science : a Publication of the Protein Society·R BoetzelG R Moore
Mar 10, 2007·Microbiology and Molecular Biology Reviews : MMBR·Eric CascalesDanièle Cavard
Aug 10, 2010·BMC Structural Biology·Andrea ZenRuth Nussinov
Feb 7, 2002·Proceedings of the National Academy of Sciences of the United States of America·Stephen L SlatinDenis Duché
May 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Buyong MaRuth Nussinov
Sep 18, 2014·BMC Bioinformatics·Prashant ShingateRamanathan Sowdhamini
Mar 27, 2004·Protein Science : a Publication of the Protein Society·Ozlem KeskinRuth Nussinov
Jun 12, 2008·Biopolymers·Sergio E WongJ Andrew McCammon
Aug 20, 2005·Journal of Molecular Biology·Anthony H Keeble, Colin Kleanthous
Feb 7, 2012·Journal of Molecular Biology·Justyna Aleksandra WojdylaColin Kleanthous
Feb 13, 2007·Structure·Ramzi Alsallaq, Huan-Xiang Zhou
Dec 10, 2014·Physical Chemistry Chemical Physics : PCCP·Irina S MoreiraPedro A Fernandes
May 16, 2001·Journal of Molecular Biology·C T EggersC S Craik
Dec 13, 2018·Nature Communications·Ravit NetzerSarel J Fleishman
May 1, 2018·Journal of Computational Chemistry·Yaqian WangXiao He
Nov 5, 2008·Journal of the American Chemical Society·Rinaldo W MontalvaoMichele Vendruscolo

❮ 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.