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The crystal structure of TGF‐β3 and comparison to TGF‐β2: Implications for receptor binding
Author(s) -
Mittl Peer R. E.,
Priestle John P.,
Cox David A.,
Mcmaster Gary,
Cerletti Nico,
Grütter Markus G.
Publication year - 1996
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560050705
Subject(s) - transforming growth factor , receptor , r smad , biophysics , chemistry , microbiology and biotechnology , cancer research , biology , tgf alpha , biochemistry , growth factor
Transforming growth factors β belong to a group of cytokines that control cellular proliferation and differentiation. Five isoforms are known that share approximately 75% sequence identity, but exert different biological activities. The structure of TGF‐β3 was solved by X‐ray crystallography and refined to a final R ‐factor of 17.5% at 2.0 Å resolution. Comparison with the structure of TGF‐β2 (Schlunegger MP, Grütter MG, 1992, Nature 358 :430‐434; Daopin S, Piez KA, Ogawa Y, Davies DR, 1992, Science 257 :369‐373) reveals a virtually identical central core. Differences exist in the conformations of the N‐terminal α‐helix and in the β‐sheet loops. In TGF‐β3, the N‐terminal α‐helix has moved ≈ 1 Å away from the central core. This movement can be correlated with the mutation of Leu 17 to Val and Ala 47 to Pro in TGF‐β3. The β‐sheet loops rotate as a rigid body 9° around an axis that runs approximately parallel to the dimer axis. If these differences are recognized by the TGF‐β receptors, they might account for the individual cellular responses. A molecule of the precipitating agent dioxane is bound in a crystal contact, forming a hydrogen bond with Trp 32. This dioxane may occupy a carbohydrate‐binding site, because dioxane possesses some structural similarity with a carbohydrate. The dioxane is in contact with two tryptophans, which are often involved in carbohydrate recognition.