Biophysical characterization reveals structural disorder in the developmental transcriptional regulator LBH

被引:28
作者
Al-Ali, Hassan [1 ]
Rieger, Megan E. [1 ,2 ]
Seldeen, Kenneth L. [1 ,2 ]
Harris, Thomas K. [1 ]
Farooq, Amjad [1 ,2 ]
Briegel, Karoline J. [1 ,2 ]
机构
[1] Univ Miami, Miller Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA
[2] Univ Miami, Miller Sch Med, Braman Family Breast Canc Inst, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA
关键词
Vertebrates; LBH; Transcriptional regulation; Embryonic development; Intrinsically disordered proteins; INTRINSIC DISORDER; PROTEIN; SPECTRA;
D O I
10.1016/j.bbrc.2009.12.032
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:1104 / 1109
页数:6
相关论文
共 20 条
[1]   A human homolog of mouse Lbh gene, hLBH, expresses in heart and activates SRE and AP-1 mediated MAPK signaling pathway [J].
Ai, Jianping ;
Wang, Yuequn ;
Tan, Kunrong ;
Deng, Yun ;
Luo, Na ;
Yuan, Wuzhou ;
Wang, Zequn ;
Li, Yongqing ;
Wang, Ying ;
Mo, Xiaoyang ;
Zhu, Chuanbing ;
Yin, Zhaochu ;
Liu, Mingyao ;
Wu, Xiushan .
MOLECULAR BIOLOGY REPORTS, 2008, 35 (02) :179-187
[2]   Congenital heart disease reminiscent of partial trisomy 2p syndrome in mice transgenic for the transcription factor Lbh [J].
Briegel, KJ ;
Baldwin, HS ;
Epstein, JA ;
Joyner, AL .
DEVELOPMENT, 2005, 132 (14) :3305-3316
[3]   Identification and characterization of Lbh, a novel conserved nuclear protein expressed during early limb and heart development [J].
Briegel, KJ ;
Joyner, AL .
DEVELOPMENTAL BIOLOGY, 2001, 233 (02) :291-304
[4]   The transcriptional cofactor Lbh regulates angiogenesis and endochondral bone formation during fetal bone development [J].
Conen, K. L. ;
Nishimori, S. ;
Provot, S. ;
Kronenberg, H. M. .
DEVELOPMENTAL BIOLOGY, 2009, 333 (02) :348-358
[5]   NMRPIPE - A MULTIDIMENSIONAL SPECTRAL PROCESSING SYSTEM BASED ON UNIX PIPES [J].
DELAGLIO, F ;
GRZESIEK, S ;
VUISTER, GW ;
ZHU, G ;
PFEIFER, J ;
BAX, A .
JOURNAL OF BIOMOLECULAR NMR, 1995, 6 (03) :277-293
[6]   Flexible nets - The roles of intrinsic disorder in protein interaction networks [J].
Dunker, AK ;
Cortese, MS ;
Romero, P ;
Iakoucheva, LM ;
Uversky, VN .
FEBS JOURNAL, 2005, 272 (20) :5129-5148
[7]   Natively unfolded proteins [J].
Fink, AL .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 2005, 15 (01) :35-41
[8]   Malleable machines take shape in eukaryotic transcriptional regulation [J].
Fuxreiter, Monika ;
Tompa, Peter ;
Simon, Istvan ;
Uversky, Vladimir N. ;
Hansen, Jeffrey C. ;
Asturias, Francisco J. .
NATURE CHEMICAL BIOLOGY, 2008, 4 (12) :728-737
[9]   Intrinsic disorder in cell-signaling and cancer-associated proteins [J].
Iakoucheva, LM ;
Brown, CJ ;
Lawson, JD ;
Obradovic, Z ;
Dunker, AK .
JOURNAL OF MOLECULAR BIOLOGY, 2002, 323 (03) :573-584
[10]  
Li, 1999, Genome Inform Ser Workshop Genome Inform, V10, P30