Structural basis for the guanine nucleotide-binding activity of tissue transglutaminase and its regulation of transamidation activity.
Tissue transglutaminase (TG) is a Ca2+-dependent acyltransferase with roles in cellular differentiation, apoptosis, and other biological functions. In addition to being a transamidase, TG undergoes a GTP-binding/GTPase cycle even though it lacks any obvious sequence similarity with canonical GTP-binding (G) proteins. Guanine nucleotide binding and Ca2+ concentration reciprocally regulate TG's transamidation activity, with nucleotide binding being the negative regulator. Here we report the x-ray structure determined to 2.8-A resolution of human TG complexed with GDP. Although the transamidation active site is similar to those of other known transglutaminases, the guanine nucleotide-binding site of TG differs markedly from other G proteins. The structure suggests a structural basis for the negative regulation of transamidation activity by bound nucleotide, and the positive regulation of transamidation by Ca2+.
Liu
Shenping
S
Department of Chemistry, Cornell University, Ithaca, NY 14853, USA.
Cerione
Richard A
RA
Clardy
Jon
J
D000595:Amino Acid Sequence; D001665:Binding Sites; D006153:Guanosine Diphosphate / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D011503:Transglutaminases / Q000737:chemistry / Q000378:metabolism*
D006153:Guanosine Diphosphate; D011503:Transglutaminases