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Investigating the structural flexibility of intrinsically disordered proteins
Author(s) -
Grese Laura Nicole,
Stanley Christopher,
Rowe Erica,
O'Neill Hugh,
Berthelier Valerie
Publication year - 2010
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.24.1_supplement.684.8
Subject(s) - intrinsically disordered proteins , computational biology , biophysics , chemistry , biology , microbiology and biotechnology
Intrinsically disordered proteins (IDPs) either possess an unstructured domain or are fully disordered until recognizing a target binding partner, upon which a coupled folding‐binding event occurs. Exactly how this mechanism is linked to protein signaling and recognition is still poorly understood, primarily because the structural flexibility of IDPs limits the number of suitable characterization techniques. We are using circular dichroism (CD) spectroscopy and small‐angle neutron scattering (SANS) to investigate IDP regions of the transcription co‐activator: CREB binding protein (CBP), and its interactions with the binding partner: activator for thyroid hormone and retinoid receptors (ACTR). CBP is essential to several biological processes such as embryonic development, growth control, and homeostasis, and its dysfunction is implicated in Huntington's disease and some cancers. CD spectroscopy allows us to study changes in protein secondary structure. With SANS we are able to directly probe structural changes on the nanometer length‐scale and in solution, which is essential for capturing the flexibility of IDP structures. SANS experiments have been performed using the BioSANS instrument at HFIR, ORNL to characterize the CBP‐ACTR complex. Ultimately, this research should provide new possibilities for the study of disordered protein regions and yield unique insights into the mechanism of IDP function. This research is supported by a Laboratory Directed Research and Development (LDRD) grant from Oak Ridge National Laboratory, managed by UT‐Battelle for the Department of Energy.