Two distinct domains within CIITA mediate self-association: involvement of the GTP-binding and leucine-rich repeat domains.
CIITA is the master regulator of class II major histocompatibility complex gene expression. We present evidence that CIITA can self-associate via two domains: the C terminus (amino acids 700 to 1130) and the GTP-binding domain (amino acids 336 to 702). Heterotypic and homotypic interactions are observed between these two regions. Deletions within the GTP-binding domain that reduce GTP-binding and transactivation function also reduce self-association. In addition, two leucine residues in the C-terminal leucine-rich repeat region are critical for self-association as well as function. This study reveals for the first time a complex pattern of CIITA self-association. These interactions are discussed with regard to the apoptosis signaling proteins, Apaf-1 and Nod1, which share domain arrangements similar to those of CIITA.
Linhoff
M W
MW
Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, 27599-7295, USA.
Harton
J A
JA
Cressman
D E
DE
Martin
B K
BK
Ting
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D002874:Chromosome Mapping; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D000090263:Leucine-Rich Repeat Proteins; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009687:Nuclear Proteins; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D000090263:Leucine-Rich Repeat Proteins; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D006160:Guanosine Triphosphate; D007930:Leucine