1 research outputs found
Structural disorder and local order of hNopp140
Human nucleolar phosphoprotein p140 (hNopp 140) is a highly phosphorylated protein inhibitor of casein
kinase 2 (CK2). As in the case of many kinase-inhibitor systems, the inhibitor has been described to belong to
the family of intrinsically disordered proteins (IDPs), which often utilize transient structural elements to bind
their cognate enzyme. Here we investigated the structural status of this protein both to provide distinct lines
of evidence for its disorder and to point out its transient structure potentially involved in interactions and
also its tendency to aggregate. Structural disorder of hNopp140 is apparent by its anomalous electrophoretic
mobility, protease sensitivity, heat stability, hydrodynamic behavior on size-exclusion chromatography, 1HNMR
spectrum and differential scanning calorimetry scan. hNopp140 has a significant tendency to aggregate and the
change of its circular dichroism spectrum in the presence of 0–80% TFE suggests a tendency to formlocal helical
structures.Wide-line NMRmeasurements suggest the overall disordered character of the protein. In all, our data
suggest that this protein falls into the pre-molten globule state of IDPs, with a significant tendency to become
ordered in the presence of its partner as demonstrated in the presence of transcription factor IIB (TFIIB)