Quantitative determination of the conformational properties of partially folded and intrinsically disordered proteins using NMR dipolar couplings.
Intrinsically disordered proteins (IDPs) inhabit a conformational landscape that is too complex to be described by classical structural biology, posing an entirely new set of questions concerning the molecular understanding of functional biology. The characterization of the conformational properties of IDPs, and the elucidation of the role they play in molecular function, is therefore one of the major challenges remaining for modern structural biology. NMR is the technique of choice for studying this class of proteins, providing information about structure, flexibility, and interactions at atomic resolution even in completely disordered states. In particular, residual dipolar couplings (RDCs) have been shown to be uniquely sensitive and powerful tools for characterizing local and long-range structural behavior in disordered proteins. In this review we describe recent applications of RDCs to quantitatively describe the level of local structure and transient long-range order in IDPs involved in viral replication, neurodegenerative disease, and cancer.
Jensen
Malene Ringkjøbing
MR
Protein Dynamics and Flexibility, Institut de Biologie Structurale, UMR 5075 CEA-CNRS-UJF, Grenoble, France.
Markwick
Phineus R L
PR
Meier
Sebastian
S
Griesinger
Christian
C
Zweckstetter
Markus
M
Grzesiek
Stephan
S
Bernadó
Pau
P
Blackledge
Martin
M
D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011487:Protein Conformation; D017510:Protein Folding; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry
D016159:Tumor Suppressor Protein p53