Transforming Growth Factor 1: Three-Dimensional Structure in Solution and Comparison with the X-ray Structure of Tran
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- 作者：Andrew P. Hinck ; Sharon J. Archer ; Su Wen Qian ; Anita B. Roberts ; Michael B. Sporn ; James A. Weatherbee ; Monica L.-S. Tsang ; Roger Lucas ; Bo-Ling Zhang ; Jeff Wenker ; and Dennis A. Torchia
- 刊名：Biochemistry
- 出版年：1996
- 出版时间：July 2, 1996
- 年：1996
- 卷：35
- 期：26
- 页码：8517 - 8534
- 全文大小：697K
- 年卷期：v.35,no.26(July 2, 1996)
- ISSN：1520-4995
文摘
The three-dimensional solution structure of human transforminggrowth factor 
beta2.gif" BORDER=0 ALIGN="middle">1 (TGF-beta2.gif" BORDER=0 ALIGN="middle">1)has been determined using multinuclear magnetic resonance spectroscopyand a hybrid distance geometry/simulated annealing algorithm. It represents one of the firstexamples of a mammalian protein structurethat has been solved by isotopic labeling of the protein in aeukaryotic cell line and multinuclear NMRspectroscopy. The solution structure of the 25 kDadisulfide-linked TGF-beta2.gif" BORDER=0 ALIGN="middle">1 homodimer was calculatedfrom over 3200 distance and dihedral angle restraints. The finalensemble of 33 accepted structures hadno NOE or dihedral angle violations greater than 0.30 Å and 5.0
,respectively. The RMSD of backboneatoms for the ensemble of 33 structures relative to their meanstructure was 1.1 Å when all residues wereused in the alignment and 0.7 Å when loop regions were omitted.The solution structure of TGF-beta2.gif" BORDER=0 ALIGN="middle">1follows two independently determined crystal structures of TGF-beta2.gif" BORDER=0 ALIGN="middle">2(Daopin et al., 1992, 1993; Schlunegger& Grütter, 1992, 1993), providing the first opportunity toexamine structural differences between the twoisoforms at the molecular level. Although the structures are verysimilar, with an RMSD in backboneatom positions of 1.4 Å when loop regions are omitted in the alignmentand 1.9 Å when all residues areconsidered, there are several notable differences in structure andflexibility which may be related to function.The clearest example of these is in the beta2.gif" BORDER=0 ALIGN="middle">-turn from residues69-72: the turn type found in the solutionstructure of TGF-beta2.gif" BORDER=0 ALIGN="middle">1 falls into the category of type II, whereas thatpresent in the X-ray crystal structureof TGF-beta2.gif" BORDER=0 ALIGN="middle">2 is more consistent with a type I turn conformation.This may be of functional significance asstudies using TGF-beta2.gif" BORDER=0 ALIGN="middle"> chimeras and deletion mutants indicate that thisportion of the molecule may beimportant in receptor binding.
beta2.gif" BORDER=0 ALIGN="middle">1 (TGF-beta2.gif" BORDER=0 ALIGN="middle">1)has been determined using multinuclear magnetic resonance spectroscopyand a hybrid distance geometry/simulated annealing algorithm. It represents one of the firstexamples of a mammalian protein structurethat has been solved by isotopic labeling of the protein in aeukaryotic cell line and multinuclear NMRspectroscopy. The solution structure of the 25 kDadisulfide-linked TGF-beta2.gif" BORDER=0 ALIGN="middle">1 homodimer was calculatedfrom over 3200 distance and dihedral angle restraints. The finalensemble of 33 accepted structures hadno NOE or dihedral angle violations greater than 0.30 Å and 5.0,respectively. The RMSD of backboneatoms for the ensemble of 33 structures relative to their meanstructure was 1.1 Å when all residues wereused in the alignment and 0.7 Å when loop regions were omitted.The solution structure of TGF-beta2.gif" BORDER=0 ALIGN="middle">1follows two independently determined crystal structures of TGF-beta2.gif" BORDER=0 ALIGN="middle">2(Daopin et al., 1992, 1993; Schlunegger& Grütter, 1992, 1993), providing the first opportunity toexamine structural differences between the twoisoforms at the molecular level. Although the structures are verysimilar, with an RMSD in backboneatom positions of 1.4 Å when loop regions are omitted in the alignmentand 1.9 Å when all residues areconsidered, there are several notable differences in structure andflexibility which may be related to function.The clearest example of these is in the beta2.gif" BORDER=0 ALIGN="middle">-turn from residues69-72: the turn type found in the solutionstructure of TGF-beta2.gif" BORDER=0 ALIGN="middle">1 falls into the category of type II, whereas thatpresent in the X-ray crystal structureof TGF-beta2.gif" BORDER=0 ALIGN="middle">2 is more consistent with a type I turn conformation.This may be of functional significance asstudies using TGF-beta2.gif" BORDER=0 ALIGN="middle"> chimeras and deletion mutants indicate that thisportion of the molecule may beimportant in receptor binding.