PMID- 8679613
OWN - NLM
STAT- MEDLINE
DCOM- 19960822
LR  - 20061115
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 35
IP  - 26
DP  - 1996 Jul 2
TI  - Transforming growth factor beta 1: three-dimensional structure in solution and 
      comparison with the X-ray structure of transforming growth factor beta 2.
PG  - 8517-34
AB  - 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 & Grutter, 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.
FAU - Hinck, A P
AU  - Hinck AP
AD  - Molecular Structural Biology Unit, National Institute of Dental Research, 
      National Institutes of Health, Bethesda, Maryland 20892-4326, USA.
FAU - Archer, S J
AU  - Archer SJ
FAU - Qian, S W
AU  - Qian SW
FAU - Roberts, A B
AU  - Roberts AB
FAU - Sporn, M B
AU  - Sporn MB
FAU - Weatherbee, J A
AU  - Weatherbee JA
FAU - Tsang, M L
AU  - Tsang ML
FAU - Lucas, R
AU  - Lucas R
FAU - Zhang, B L
AU  - Zhang BL
FAU - Wenker, J
AU  - Wenker J
FAU - Torchia, D A
AU  - Torchia DA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Amides)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Amides/chemistry
MH  - Amino Acid Sequence
MH  - Animals
MH  - Humans
MH  - Hydrogen Bonding
MH  - Magnetic Resonance Spectroscopy
MH  - Molecular Sequence Data
MH  - Protein Conformation
MH  - Sequence Homology, Amino Acid
MH  - Transforming Growth Factor beta/*chemistry
MH  - X-Ray Diffraction
EDAT- 1996/07/02 00:00
MHDA- 1996/07/02 00:01
CRDT- 1996/07/02 00:00
PHST- 1996/07/02 00:00 [pubmed]
PHST- 1996/07/02 00:01 [medline]
PHST- 1996/07/02 00:00 [entrez]
AID - bi9604946 [pii]
AID - 10.1021/bi9604946 [doi]
PST - ppublish
SO  - Biochemistry. 1996 Jul 2;35(26):8517-34. doi: 10.1021/bi9604946.