Intrinsically disordered proteins detection

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. 

Hereditary spherocytosis is a group of disorders caused by heterogeneous intrinsic defects of the red cell membrane proteins. Describe the rapid and sensitive methods to detect mutations in genomic DNA and complementary DNA. 

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