Identifizierung und Charakterisierung von neuen Genen für die ...

- 69 -
Bei TRIM46 allerdings schien die RING-BBC1-BBC2-CC-Struktur alleine nicht auszureichen, um
Protein-Protein-Interaktionen zu vermitteln, da mit Isoform 1 (cDNA4) im Yeast-Two-Hybrid-Screen
keine Protein-Partner gefunden wurden, wohl aber für Isoform 2 (cDNA12, siehe ab Seite 75).
“There are two different variants, the C3HC4-type and a C3H2C3-type, which is clearly related despite
the different cysteine/histidine pattern. The latter type is sometimes referred to as 'RING-H2 finger'.”
“Several 3D-structures for RING-fingers are
known. The 3D structure of the zinc ligation
system is unique to the RING domain and is
referred to as the 'cross-brace' motif. The
spacing of the cysteines in such a domain is
C-x(2)-C-x(9 to 39)-C-x(1 to 3)-H-x(2 to 3)-
C-x(2)-C-x(4 to 48)-C-x(2)-C. Metal ligand
pairs one and three co-ordinate to bind one
zinc ion, whilst pairs two and four bind the
second, as illustrated”.
“Note that in the older literature, some RING-fingers are denoted as LIM-domains. The LIM-domain Znfinger
is a fundamentally different family, albeit with similar Cys-spacing”.
“Diseases involved in mutations with the RING-Domain”:
“Zellweger syndrome (Peroxisome Biogenesis Factor 10; PEX10, lethal diseases that are characterized by
neuronal, hepatic, and renal abnormalities and severe mental retardation), Adrenoleukodystrophy
neonatal, Breast cancer-1 (Breast Cancer 1 Gene; BRCA1); Ovarian cancer; Breast-ovarian cancer;
Papillary serous carcinoma of the peritoneum, Prostate cancer.”
BBox:
“The B-box zinc finger is an around 40 amino acids domain. One or two copies of this motif are
generally associated with a ring finger and a coiled coil motif to form the so-called tripartite motif. It
is found essentially in transcription factors, ribonucleoproteins and protooncoproteins, but no
function is clearly assigned to this domain. It has been shown to be essential but not sufficient to
localize the PML protein in a punctate pattern in interphase nuclei . Among the 7 possible ligands for the
zinc atom contained in a B-box, only 4 are used and bind one zinc atom in a Cys2-His2 tetrahedral
arrangement. The NMR analysis reveals that the B-box structure comprises two beta-strands, two helical
turns and three extended loop regions different from any other zinc binding motif.”
“Diseases involved in mutations with the BBox-Domain”:
“Familial Mediterranean fever (Pyrin / Marenostrin) is an autosomal recessive disorder characterized by
recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by
pain. Amyloidosis with renal failure is a complication and may develop without overt crises”.
BBC BBox-C-terminal:
“Coiled coil region C-terminal to (some) B-Box domains.
It is found in transcription intermediary factor 1-alpha, which associates with DNA-bound estrogen
receptors; ring finger protein, a putative transcriptional regulator; and the GTP-binding protein Ard-1.”