The Importance of Being Flexible: The Case of Basic Region Leucine Zipper Transcriptional Regulators
Pp. 493-558 (66)
Large volumes of protein sequence and structure data acquired by proteomic
studies led to the development of computational bioinformatic techniques that made
possible the functional annotation and structural characterization of proteins based on
their primary structure. It has become evident from genome-wide analyses that many
proteins in eukaryotic cells are either completely disordered or contain long
unstructured regions that are crucial for their biological functions. The content of
disorder increases with evolution indicating a possibly important role of disorder in the
regulation of cellular systems. Transcription factors are no exception and several
proteins of this class have recently been characterized as premolten/molten globules.
Yet, mammalian cells rely on these proteins to control expression of their 30,000 or so
genes. Basic region: leucine zipper (bZIP) DNA-binding proteins constitute a major
class of eukaryotic transcriptional regulators. This review discusses how conformational
flexibility “built” into the amino acid sequence allows bZIP proteins to interact with a
large number of diverse molecular partners and to accomplish their manifold cellular
tasks in a strictly regulated and coordinated manner.
bZIP proteins, transcription control, intrinsic disorder, sequence
analysis, disorder predictors, natively-unfolded proteins, partially folded proteins,
induced protein folding, molecular recognition motifs, protein-protein interactions,
protein-DNA interactions, transient interactions, binding affinity, binding specificity,
protein functional domains, bZIP oligomerization, combinatorial gene regulation,
transcription coregulator complexes, cellulat networks, signaling.
Macromolecular Crystallography Laboratory; Center for Cancer Research, National Cancer Institute-Frederick Frederick, MD, 21702-1201.