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PDBsum entry 1kld
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Growth factor
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PDB id
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1kld
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Transforming growth factor beta 1: three-Dimensional structure in solution and comparison with the X-Ray structure of transforming growth factor beta 2.
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Authors
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A.P.Hinck,
S.J.Archer,
S.W.Qian,
A.B.Roberts,
M.B.Sporn,
J.A.Weatherbee,
M.L.Tsang,
R.Lucas,
B.L.Zhang,
J.Wenker,
D.A.Torchia.
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Ref.
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Biochemistry, 1996,
35,
8517-8534.
[DOI no: ]
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PubMed id
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Abstract
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The three-dimensional solution structure of human transforming growth factor
beta 1 (TGF-beta 1) has been determined using multinuclear magnetic resonance
spectroscopy and a hybrid distance geometry/ simulated annealing algorithm. It
represents one of the first examples of a mammalian protein structure that has
been solved by isotopic labeling of the protein in a eukaryotic cell line and
multinuclear NMR spectroscopy. The solution structure of the 25 kDa
disulfide-linked TGF-beta 1 homodimer was calculated from over 3200 distance and
dihedral angle restraints. The final ensemble of 33 accepted structures had no
NOE or dihedral angle violations greater than 0.30 A and 5.0 degrees,
respectively. The RMSD of backbone atoms for the ensemble of 33 structures
relative to their mean structure was 1.1 A when all residues were used in the
alignment and 0.7 A when loop regions were omitted. The solution structure of
TGF-beta 1 follows two independently determined crystal structures of TGF-beta 2
(Daopin et al., 1992, 1993; Schlunegger & Grütter, 1992, 1993), providing
the first opportunity to examine structural differences between the two isoforms
at the molecular level. Although the structures are very similar, with an RMSD
in backbone atom positions of 1.4 A when loop regions are omitted in the
alignment and 1.9 A when all residues are considered, there are several notable
differences in structure and flexibility which may be related to function. The
clearest example of these is in the beta-turn from residues 69-72: the turn type
found in the solution structure of TGF-beta 1 falls into the category of type
II, whereas that present in the X-ray crystal structure of TGF-beta 2 is more
consistent with a type I turn conformation. This may be of functional
significance as studies using TGF-beta chimeras and deletion mutants indicate
that this portion of the molecule may be important in receptor binding.
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