Calorimetric dissection of colicin DNase--immunity protein complex specificity

Biochemistry
Anthony H KeebleColin Kleanthous

Abstract

We explore the thermodynamic strategies used to achieve specific, high-affinity binding within a family of conserved protein-protein complexes. Protein-protein interactions are often stabilized by a conserved interfacial hotspot that serves as the anchor for the complex, with neighboring variable residues providing specificity. A key question for such complexes is the thermodynamic basis for specificity given the dominance of the hotspot. We address this question using, as our model, colicin endonuclease (DNase)-immunity (Im) protein complexes. In this system, cognate and noncognate complexes alike share the same mechanism of association and binding hotspot, but cognate complexes (K(d) approximately 10(-)(14) M) are orders of magnitude more stable than noncognate complexes (10(6)-10(10)-fold discrimination), largely because of a much slower rate of dissociation. Using isothermal titration calorimetry (ITC), we investigated the changes in enthalpy (DeltaH), entropy (-TDeltaS), and heat capacity (DeltaC(p)) accompanying binding of each Im protein (Im2, Im7, Im8, and Im9) to the DNase domains of colicins E2, E7, E8, and E9, in the context of both cognate and noncognate complexes. The data show that specific binding to the E2, E7, ...Continue Reading

References

Mar 20, 1992·Journal of Molecular Biology·J Foote, G Winter
Sep 22, 1995·Journal of Molecular Biology·J Gómez, E Freire
Sep 10, 1999·The Journal of Biological Chemistry·J A WibbenmeyerR C Willson
Sep 10, 1999·The Journal of Biological Chemistry·A J PommerC Kleanthous
Dec 6, 2001·Journal of Molecular Biology·A J PommerC Kleanthous
Apr 21, 2004·Journal of Molecular Biology·Simon BergqvistJohn E Ladbury
Jul 9, 2004·Journal of Molecular Biology·Christina KielChristian Herrmann
Aug 20, 2005·Journal of Molecular Biology·Anthony H Keeble, Colin Kleanthous

❮ Previous
Next ❯

Citations

Nov 17, 2011·Quarterly Reviews of Biophysics·Grigorios PapadakosColin Kleanthous
May 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Nicola A G MeenanColin Kleanthous
Mar 10, 2007·Microbiology and Molecular Biology Reviews : MMBR·Eric CascalesDanièle Cavard
Oct 11, 2007·BMC Biology·Alexandra Shulman-PelegHaim J Wolfson
Oct 15, 2014·Journal of Molecular Biology·Shira WarszawskiSarel J Fleishman
Jan 18, 2008·Journal of Molecular Recognition : JMR·Oksana Okhrimenko, Ilian Jelesarov
Jun 12, 2008·Biopolymers·Sergio E WongJ Andrew McCammon
Jul 8, 2010·Proteins·Miriam EisensteinNoga Kowalsman
Jan 8, 2011·Protein Science : a Publication of the Protein Society·Panagiotis L KastritisJoël Janin
Jan 10, 2012·Journal of Molecular Biology·Clare L PashleySheena E Radford
Feb 7, 2012·Journal of Molecular Biology·Justyna Aleksandra WojdylaColin Kleanthous
Jan 24, 2007·Current Opinion in Structural Biology·Dana ReichmannGideon Schreiber
Sep 6, 2012·Biophysical Journal·Krishnakumar M RavikumarSichun Yang
Aug 11, 2007·The Journal of Biological Chemistry·Candice S E LengyelBenjamin J McFarland
Dec 13, 2018·Nature Communications·Ravit NetzerSarel J Fleishman
Jan 9, 2020·Journal of Chemical Theory and Computation·Stefano PianaDavid E Shaw
Sep 18, 2021·Frontiers in Molecular Biosciences·Uroš ZavrtanikJurij Lah
Aug 4, 2007·Journal of the American Chemical Society·Mrinmoy DeVincent M Rotello

❮ 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.