Biophysical characterization reveals structural disorder in the developmental transcriptional regulator LBH.
Limb-bud and heart (LBH) is a key transcriptional regulator in vertebrates with pivotal roles in embryonic development and human disease. Herein, using a diverse array of biophysical techniques, we report the first structural characterization of LBH pertinent to its biological function. Our data reveal that LBH is structurally disordered with no discernable secondary or tertiary structure and exudes rod-like properties in solution. Consistent with these observations, we also demonstrate that LBH is conformationally flexible and thus may be capable of adapting distinct conformations under specific physiological contexts. We propose that LBH is a member of the intrinsically disordered protein (IDP) family, and that conformational plasticity may play a significant role in modulating LBH-dependent transcriptional processes.
Al-Ali
Hassan
H
Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Rieger
Megan E
ME
Seldeen
Kenneth L
KL
Harris
Thomas K
TK
Farooq
Amjad
A
Briegel
Karoline J
KJ
D000595:Amino Acid Sequence; D000818:Animals; D055592:Biophysical Phenomena; D018797:Cell Cycle Proteins; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors
D018797:Cell Cycle Proteins; C428223:Lbh protein, mouse; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors