Residual Structure in Intrinsically Disordered Proteins

The topic of intrinsically disordered proteins is covered in detail in Chapter 17. It is also discussed briefly here, however, because the characterization of residual structure in the native conformational ensembles of intrinsically disordered proteins is an important application of millisecond HX. 

Intrinsically disordered proteins adopt a broad, but bounded distribution of structures under physiological conditions [59]. While much of the sequence is often fully disordered, there are also regions where the ensemble tends to transiently form specific secondary and/or tertiary stractures, known as residual structure. Residual structure is insufficient to attenuate HX to the point where it can be detected in conventional experiments however, it is easily detected with millisecond labeling. While a number of earlier studies hinted at the use of millisecond HX to examine residual structure (even if it was only to say that their earliest 10 s time point was inadequate to characterize disordered regions) [60, 61], the first direct reference was in a 2011 study by Keppel et al., in the investigation of the interaction between an intrinsically disordered domain and a molten globule domain to form a structured complex [4], However, this study used conventional labeling times. 

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Millisecond Hydrogen Exchange 87 5.4.5 Residual Structure in Intrinsically Disordered Proteins... 

Keppel, T.R., Weis, DD. (2015) Mapping Residual Structure in Intrinsically Disordered Proteins at Residue Resolution Using Millisecond Hydrogen/Deuterium Exchange and Residue Averaging. J. Am. Soc. Mass Spectrom. 26 547-554. 

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