Ribonuclease A contains two exposed loop regions, around Ala20 andAsn34. Only the loop aroundAla20 is sufficiently flexible even under native conditions to allow cleavage by nonspecific proteases. In contrast, the loop around Asn34 (together with the adjacentb-sheet aroundThr45) is the first region of the ribonuclease A molecule that becomes sus-ceptible to thermolysin and trypsin under unfolding condi-tions. This second region therefore has been suggested to be involved in early steps of unfolding and was designated as the unfolding region of the ribonuclease A molecule
