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A cis‐proline in the hinge region of RNase A acts as a conformational gatekeeper for domain‐swapping
Author(s) -
Karr Jessica,
Miller Katherine,
Marqusee Susan
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.863.11
Subject(s) - proline , isomerization , hinge , dimer , chemistry , rnase p , protein folding , biophysics , folding (dsp implementation) , monomer , stereochemistry , protein structure , crystallography , biochemistry , amino acid , biology , rna , physics , catalysis , polymer , organic chemistry , electrical engineering , engineering , classical mechanics , gene
Three‐dimensional domain swapping has been implicated in a wide range of functions including evolution of quaternary structure, activity regulation, and protein aggregation and amyloid formation. While the structural consequences of domain swapping have been well documented, little is understood about the specific structural and energetic features that cause this unique folding phenomenon to occur. An increased frequency of proline residues has been observed in hinge regions preceding swapped structural units, implying that the cis‐trans isomerization of proline may play an important role in domain swapping. For example, a trans proline may help extend the swapped arm, making it more accessible for exchange, while a cis‐proline may act as a conformational gatekeeper to prevent domain swapping by biasing the swapped arm towards contacts with the core of its own monomeric unit. Using RNase A as a model system, we have examined the role of a hinge region proline that undergoes cis to trans isomerization as the protein forms a domain‐swapped dimer. Results suggest that replacing the cis‐proline in the hinge region with a residue that energetically favors a trans configuration dramatically increases the ability of RNase A to form domain‐swapped dimers under physiological conditions.