Noble M E, Musacchio A, Saraste M, Courtneidge S A, Wierenga R K
EMBL, Heidelberg, Germany.
EMBO J. 1993 Jul;12(7):2617-24. doi: 10.2210/pdb1shf/pdb.
The Src-homology 3 (SH3) region is a protein domain consisting of approximately 60 residues. It occurs in a large number of eukaryotic proteins involved in signal transduction, cell polarization and membrane--cytoskeleton interactions. The function is unknown, but it is probably involved in specific protein--protein interactions. Here we report the crystal structure of the SH3 domain of Fyn (a Src family tyrosine kinase) at 1.9 A resolution. The crystals have two SH3 molecules per asymmetric unit. These two Fyn SH3 domains are not related by a local twofold axis. The crystal structures of spectrin and Fyn SH3 domains as well as the solution structure of the Src SH3 domain show that these all have the same basic fold. A protein domain which has the same topology as SH3 is present in the prokaryotic regulatory enzyme BirA. The comparison between the crystal structures of Fyn and spectrin SH3 domains shows that a conserved surface patch, consisting mainly of aromatic residues, is flanked by two hairpin-like loops (residues 94-104 and 114-118 in Fyn). These loops are different in tyrosine kinase and spectrin SH3 domains. They could modulate the binding properties of the aromatic surface.
Src同源3（SH3）区域是一个由大约60个氨基酸残基组成的蛋白质结构域。它存在于大量参与信号转导、细胞极化和膜-细胞骨架相互作用的真核生物蛋白质中。其功能尚不清楚，但可能参与特定的蛋白质-蛋白质相互作用。在此，我们报道了Fyn（一种Src家族酪氨酸激酶）的SH3结构域在1.9埃分辨率下的晶体结构。每个不对称单元的晶体中有两个SH3分子。这两个Fyn SH3结构域不存在局部二重对称轴关系。血影蛋白和Fyn SH3结构域的晶体结构以及Src SH3结构域的溶液结构表明，它们都具有相同的基本折叠。原核调节酶BirA中存在一个与SH3拓扑结构相同的蛋白质结构域。Fyn和血影蛋白SH3结构域晶体结构的比较表明，一个主要由芳香族残基组成的保守表面区域两侧是两个发夹样环（Fyn中的94-104和114-118位残基）。这些环在酪氨酸激酶和血影蛋白SH3结构域中有所不同。它们可能调节芳香族表面的结合特性。
