| Abstract: | The crystal structure of TGF-β2 has been refined using data collected with synchrotron radiation (CHESS) to 1.8 Å resolution with a residual R (= ∑ | |Fo| ? |Fc| | /∑ |Fo|) factor of 17.3%. The model consists of 890 protein atoms from all 112 residues and 59 water molecules. The monomer of TGF-β2 assumes a rather extended conformation and lacks a well-defined hydrophobic core. Surface accessibility calculations show only 44% of the nonpolar surface is buried in the monomer. In contrast, 55.8% of the nonpolar surface area is buried when the two monomers from a dimer, a typical value for globular proteins. This includes a 1300 Å2 buried interface area that is largely hydrophobic. Sequence comparisons using a profile derived from the refined TGF-β2 structure suggest that the cluster of four disulfides (three intramonomeric disulfide bonds 15–78, 44–109, 48–111 forming a disulfide knot, and one intermonomeric disulfide 77–77) together with the extended β strand region constitutes the conserved structural motif for the TGF-β superfamily. This structural motif, without the 77–77 disulfide bond, defines also the common fold for a general family of growth factors, including the nerve growth factor and platelet-derived growth factor families. The fold is conserved only at the monomer level, while the active forms are dimers, suggesting that dimerization plays an important role in regulating the binding of these cytokines to their receptors and in modulating the biological responses. © 1993 Wiley-Liss, Inc. 1 This article is a US Government work and, as such, is in the public domain in the United States of America. |
