Structural characterization of the N-terminal region of Streptococcus pneumonia surface protein C

Cullin3 (Cul3) is an ubiquitin E3 ligase responsible for catalyzing the transfer of an ubiquitin moiety from an E2 enzyme to a target substrate protein. The C-terminal region of Cul3 binds RBX1/E2-ubiquitin, while, the N-terminal region interacts with various BTB domain proteins which serve as substrate adaptors. Previously, our group determined the crystal structures of the homodimeric BTB proteins SPOP and KLHL3 in complex with the N-terminal domain of Cul3, revealing the determinants responsible for the BTB/Cul3 interaction [1, 2]. A second class of BTB-domain containing proteins, the KCTD proteins, are also Cul3 substrate adaptors but these do not share many of the previously determined features for Cul3 binding. Furthermore, KCTD proteins form homotetramers and homopentamers via BTB oligomerization rather than the previously described homodimers. Despite these differences, many KCTD proteins interact with Cul3 with dissociation constants of approximately 50 nM. While the target substrates for many of the KCTD/Cul3 E3 ligase complexes are unknown, recent studies have implicated the GABAβ2 receptor as an interactor of KCTD 8, 12, 12b and 16. Here, we report the pentameric crystal structure of the KCTD9 BTB domain and our progress on the structural characterization of Cul3/KCTD/substrate complexes.

Download Full-text

Structural Characterization of the Gene for Human Histidine-Rich Glycoprotein, Reinvestigation of the 5'-Terminal Region of cDNA and a Search for the Liver Specific Promoter in the Gene

The Journal of Biochemistry ◽

10.1093/oxfordjournals.jbchem.a022316 ◽

1999 ◽

Vol 125 (3) ◽

pp. 522-530 ◽

Cited By ~ 5

Author(s):

S. Wakabayashi ◽

K. Takahashi ◽

T. Koide

Keyword(s):

Structural Characterization ◽

Terminal Region

Download Full-text

Structural characterization of the Borrelia burgdorferi outer surface protein BBA73 implicates dimerization as a functional mechanism

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2013.04.028 ◽

2013 ◽

Vol 434 (4) ◽

pp. 848-853 ◽

Cited By ~ 7

Author(s):

Kalvis Brangulis ◽

Ivars Petrovskis ◽

Andris Kazaks ◽

Viesturs Baumanis ◽

Kaspars Tars

Keyword(s):

Borrelia Burgdorferi ◽

Structural Characterization ◽

Outer Surface ◽

Surface Protein ◽

Functional Mechanism ◽

Outer Surface Protein

Download Full-text

Characterization of Naturally Acquired Human IgG Responses against the N-Terminal Region of the Merozoite Surface Protein 1 of Plasmodium vivax

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.1994.51.68 ◽

1994 ◽

Vol 51 (1) ◽

pp. 68-76 ◽

Cited By ~ 20

Author(s):

Gabriela Levitus ◽

Marcia A. Speranca ◽

Luis Marcelo Aranha Camargo ◽

Marcelo Urbano Ferreira ◽

Frederic Mertens ◽

...

Keyword(s):

Plasmodium Vivax ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Terminal Region ◽

Human Igg ◽

Merozoite Surface Protein 1

Download Full-text

The Dominant Epitope of Borrelia garinii Outer Surface Protein C Recognized by Sera from Patients with Neuroborreliosis Has a Surface-Exposed Conserved Structural Motif

Infection and Immunity ◽

10.1128/iai.66.9.4073-4079.1998 ◽

1998 ◽

Vol 66 (9) ◽

pp. 4073-4079 ◽

Cited By ~ 31

Author(s):

Marianne J. Mathiesen ◽

Arne Holm ◽

Michael Christiansen ◽

Jens Blom ◽

Klaus Hansen ◽

...

Keyword(s):

B Cells ◽

Lyme Borreliosis ◽

Outer Surface ◽

Protein C ◽

Surface Protein ◽

Terminal Region ◽

Structural Motif ◽

High Avidity ◽

Binding Studies ◽

Outer Surface Protein

ABSTRACT Epitope mapping of outer surface protein C (OspC) by using sera from patients with neuroborreliosis led to the identification of one single major immunodominant epitope within the C-terminal 10 amino acid residues. Peptide binding studies and alanine replacement scanning of the C-terminal decapeptide, PVVAESPKKP, revealed a critical role for the PKKP sequence and its terminal carboxyl group for the binding of immunoglobulin M (IgM) antibodies from patients with Lyme borreliosis. Electron microscopy of antibody-labeled spirochetes indicated that the C-terminal region is exposed on the surface of the spirochete. Based on homology to proteins of known function, this region most probably adopts a polyproline II-like helix, which is found in surface-exposed structures involved in protein-protein interactions. This structural motif is highly conserved in Borrelia species causing Lyme borreliosis and subjected to purifying selection. We suggest that the abundance of the C-terminal region of OspC on the surface of B. burgdorferi allows a multimeric high-avidity interaction between the spirochete and surface Igs on B cells. The resulting cross-linking of surface Igs on B cells may induce a T-cell-independent B-cell activation without IgM-to-IgG switching, thus explaining the lack of IgG antibodies to OspC in neuroborreliosis.

Download Full-text