Abstract:
:A substantial fraction of the human proteome encodes disordered proteins. Protein disorder is associated with a variety of cellular functions and misfunction, and is therefore of clear import to biological systems. However, disorder lends itself to conformational flexibility and heterogeneity, rendering proteins which feature prominent disorder difficult to study using conventional structural biology methods. Here we discuss a few examples of how single-molecule methods are providing new insight into the biophysics and complexity of these proteins by avoiding ensemble averaging, thereby providing direct information about the complex distributions and dynamics of this important class of proteins. Examples of note include characterization of isolated IDPs in solution as collapsed and dynamic species, detailed insight into complex IDP folding landscapes, and new information about how tunable regulation of structure-mediated binding cooperativity and consequent function can be achieved through protein disorder. With these exciting advances in view, we conclude with a discussion of a few complementary and emerging single-molecule efforts of particular promise, including complementary and enhanced methodologies for studying disorder in proteins, and experiments to investigate the potential role for IDP-induced phase separation as a critical functional element in biological systems.
journal_name
Semin Cell Dev Bioljournal_title
Seminars in cell & developmental biologyauthors
Lee T,Moran-Gutierrez CR,Deniz AAdoi
10.1016/j.semcdb.2014.09.027subject
Has Abstractpub_date
2015-01-01 00:00:00pages
26-34eissn
1084-9521issn
1096-3634pii
S1084-9521(14)00294-8journal_volume
37pub_type
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