4udm | pdb_00004udm
Crystal structure of Im3 in complex with Y52A mutant of E3RNase
Structural highlights
FunctionIMM3_ECOLX This protein inhibits the 16S RNA hydrolyzing activity of colicin E3 by binding with high affinity to the C-terminal catalytic domain of E3. This protein is able to protect a cell, which harbors the plasmid ColE3 against colicin E3. Publication Abstract from PubMedThe kinetic and thermodynamic consequences of intrinsic disorder in protein-protein recognition are controversial. We address this by inducing one partner of the high-affinity colicin E3 rRNase domain-Im3 complex (K(d) approximately 10(-12) M) to become an intrinsically disordered protein (IDP). Through a variety of biophysical measurements, we show that a single alanine mutation at Tyr507 within the hydrophobic core of the isolated colicin E3 rRNase domain causes the enzyme to become an IDP (E3 rRNase(IDP)). E3 rRNase(IDP) binds stoichiometrically to Im3 and forms a structure that is essentially identical to the wild-type complex. However, binding of E3 rRNase(IDP) to Im3 is 4 orders of magnitude weaker than that of the folded rRNase, with thermodynamic parameters reflecting the disorder-to-order transition on forming the complex. Critically, pre-steady-state kinetic analysis of the E3 rRNase(IDP)-Im3 complex demonstrates that the decrease in affinity is mostly accounted for by a drop in the electrostatically steered association rate. Our study shows that, notwithstanding the advantages intrinsic disorder brings to biological systems, this can come at severe kinetic and thermodynamic cost. Consequences of inducing intrinsic disorder in a high-affinity protein-protein interaction.,Papadakos G, Sharma A, Lancaster LE, Bowen R, Kaminska R, Leech AP, Walker D, Redfield C, Kleanthous C J Am Chem Soc. 2015 Apr 29;137(16):5252-5. doi: 10.1021/ja512607r. Epub 2015 Apr , 17. PMID:25856265[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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