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Ribonuclease A is an enzyme found in the pancreas that is involved in catalyzing RNA degradation [http://www.uta.edu/faculty/sawasthi/Enzymology-4351-5324/Class%20Syllabus%20Enzymology/ribonucleaseA.pdf].  The kidney-shaped structure of RNase A has been determined through crystallography [http://en.wikipedia.org/wiki/Crystallography] and Fast Atom Bombardment Mass Spectrometry [http://en.wikipedia.org/wiki/Fast_atom_bombardment].  FABMS is performed by mixing the material to be analyzed (RNase A) with a non-volatile environment called a matrix and is then bombarded by high energy molecules within a vacuum.  Bombardment causes the molecules to ionize so they can be detected by mass spectrometry. Through this technique it has been found that RNase A is composed of four anti-parallel β-sheets and three α-helixes. Presence of four disulfide bonds and two ''cis'' proline residues greatly effects the structure and folding kinetics of RNase A [http://nobelprize.org/nobel_prizes/chemistry/laureates/1972/anfinsen-bio.html]. When RNase A undergoes reductive denaturation, it spontaneously folds back on itself to form the same structure. This observation of ribonuclease folding helped Christian Anfinsen win the Nobel Prize in 1972 for his work on protein folding [http://nobelprize.org/nobel_prizes/chemistry/laureates/1972/anfinsen-lecture.html].

Interatomic interactions, delegated by the amino acid sequence, are responsible for formation of a protein's 3D structure [http://en.wikipedia.org/wiki/Protein_folding].  Several of these interactions have been identified by the use of site directed mutagenesis to wildtype RNase A and subsequent comparison of the crystal structure to the wildtype. Although RNase A has 105 possible disulfide bond pairings, only one occurs. This unique observation leads to the "thermodynamic hypothesis", that a protein's native state is determined by the thermodynamic favorability of he whole system; thus the tertiary structure must be predetermined by intramolecular interactions within the amino acid sequence. Since thermodynamic stability of a protein is effected by the environment's temperature, pH, and ionic strength, among other factors, the protein structure can only exist under physiological conditions. Today, the correlation between the amino acid sequence and the tertiary structure of RNase A continues to serve as a model for protein folding. Among the most important attributes of this model are noncovalent interactions, proline orientation, and disulfide bonding.

Another important role of proline residues is their involvement in β turns. β turns are 180° turns commonly found in globular proteins to allow for a compact structure by connecting the ends of adjacent antiparallel β sheets [http://en.wikipedia.org/wiki/Beta_sheet]. The turn consists of a sequence of four amino acid residues. The carbonyl of the first amino acid hydrogen bonds with the amino group of the fourth amino acid. Proline is involved in β turns because it is small, flexible, and assumes a ''cis'' conformation, all attributes that allow for formation of a turn. In RNase A both Pro93 and Pro114 are involved in β turns. Proline residues are important to protein folding because their flexibility in forming a favorable ''cis'' conformation allow for thermodynamic favorability of formation of β turns and thus allow proteins to reside in a compact, globular structure.