TY  - JOUR
A1  - Neculai, Dante
A1  - Neculai, Ana Mirela
A1  - Verrier, Sophie
A1  - Straub, Kenneth
A1  - Klumpp, Klaus
A1  - Pfitzner, Edith
A1  - Becker, Stefan
T1  - Structure of the unphosphorylated STAT5a dimer
T2  - Journal of biological chemistry
N2  - STAT proteins have the function of signaling from the cell membrane into the nucleus, where they regulate gene transcription. Latent mammalian STAT proteins can form dimers in the cytoplasm even before receptor-mediated activation by specific tyrosine phosphorylation. Here we describe the 3.21-A crystal structure of an unphosphorylated STAT5a homodimer lacking the N-terminal domain as well as the C-terminal transactivation domain. The overall structure of this fragment is very similar to phosphorylated STATs. However, important differences exist in the dimerization mode. Although the interface between phosphorylated STATs is mediated by their Src-homology 2 domains, the unphosphorylated STAT5a fragment dimerizes in a completely different manner via interactions between their beta-barrel and four-helix bundle domains. The STAT4 N-terminal domain dimer can be docked onto this STAT5a core fragment dimer based on shape and charge complementarities. The separation of the dimeric arrangement, taking place upon activation and nuclear translocation of STAT5a, is demonstrated by fluorescence resonance energy transfer experiments in living cells.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76222
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-762227
SN  - 0021-9258
VL  - 280.2005
IS  - 49
SP  - 40782
EP  - 40787
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -