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On the forces stabilizing supertertiary structure in multi‐domain proteins (770.2)
Author(s) -
Lemmon Eric,
Shanbhogue Prajna,
McCann James,
Bowen Mark
Publication year - 2014
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.28.1_supplement.770.2
Subject(s) - linker , biophysics , protein structure , pdz domain , rigidity (electromagnetism) , chemistry , crystallography , isotropy , domain (mathematical analysis) , protein domain , biological system , computer science , physics , mathematics , biology , biochemistry , mathematical analysis , quantum mechanics , gene , operating system
Many proteins are modular in that they contain a series of independently‐folded domains. Often, these sub‐domains have no affinity for each other in solution, but can maintain a stable supertertiary structure when connected by polypeptide linkers. Little is known about the ultraweak interactions that dictate the stability of supertertiary structure. It is our hypothesis that surface features select for a specific structure, while the linker length determines the effective concentration thereby setting the interaction energy. To test this we attempted to redesign the multi‐domain scaffold protein PSD‐95. Structural studies have observed a stable supertertiary structure for the two N‐terminal PDZ domains from PSD‐95, but differing structural models were unable to identify interdomain interactions. We added a new interdomain salt bridge and linker extensions of varying rigidity. These manipulations rearranged the supertertiary structure but did not lead to isotropic motion of domains. This suggests that the forces stabilizing the structure are sufficient to withstand a 1.5‐fold decrease in effective domain concentration. Grant Funding Source : Supported by NIMH Grant MH081923