Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P50583 (
asymmetrical
)
12,197
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Rat liver mannose-binding protein (
MBP-C
) is the smallest known member of the collectin family of animal lectins, many of which are involved in defence against microbial pathogens. It consists of an N-terminal collagen-like domain linked to C-terminal carbohydrate-recognition domains.
MBP-C
, overproduced in Chinese-hamster ovary cells, is post-translationally modified and processed in a manner similar to the native lectin. Analytical ultracentrifugation experiments indicate that
MBP-C
is trimeric, with a weight-averaged molecular mass of approx. 77 kDa. The rate of sedimentation of
MBP-C
and its mobility on gel filtration suggest a highly elongated molecule. Anomalous behaviour on gel filtration due to this extended conformation may explain previous suggestions that
MBP-C
forms a higher oligomer. The polypeptide chains of the
MBP-C
trimer are linked by disulphide bonds between two cysteine residues at the N-terminal junction of the collagen-like domain. Analysis of an N-terminal tryptic fragment reveals that the disulphide bonding in
MBP-C
is heterogeneous and
asymmetrical
. These results indicate that assembly of
MBP-C
oligomers probably proceeds in a C- to N-terminal direction: trimerization at the C-terminus is followed by assembly of the collagenous domain and finally formation of N-terminal disulphide bonds. The relatively simple organization of
MBP-C
provides a template for understanding larger, more complex collectins.
...
PMID:Asymmetry adjacent to the collagen-like domain in rat liver mannose-binding protein. 923 Jan 18
Rat serum mannose-binding protein (MBP-A) functions as part of the innate immune system by targetting complement toward potentially pathogenic microorganisms. In order to examine the molecular basis for complement activation, rat MBP-A has been overproduced in Chinese hamster ovary cells. Recombinant protein is post-translationally modified in the same way as the native lectin. Hydrodynamic studies indicate that MBP-A consists predominantly of covalent oligomers containing one to four copies of a subunit that comprises a trimer of polypeptides. These oligomers are non-interconverting and do not assemble into higher order structures at concentrations in excess of those normally found in serum. Disulfide bonds formed between cysteine residues at the N-terminal end of the collagen-like domain link polypeptides to form covalent oligomers. Analysis of wild-type MBP-A and MBP-A containing the substitution Cys6 --> Ser suggests that polypeptides within each trimeric structural unit are mostly linked by disulfide bonds between cysteine residues at positions 13 and 18 arranged in an
asymmetrical
configuration. Disulfide bonds involving Cys6 connect polypeptides within separate trimers. Analysis of chimeras between MBP-A and rat liver MBP (
MBP-C
) indicates that residues within the N-terminal region of the collagenous domain and the cysteine-rich domain of MBP-A enable assembly of trimers into higher order oligomers. The activity of MBP-A in a hemolytic complement fixation assay using mannan-coated sheep erythrocytes was approximately 20-fold greater than the activity of
MBP-C
. Analysis of the MBP chimeras and isolated oligomers of MBP-A reveals that the larger oligomers are more efficient at complement activation. These data indicate that the overall complement fixing activity of MBP-A is a function of the individual molecular activities of oligomers and their relative abundance within the serum.
...
PMID:Molecular determinants of oligomer formation and complement fixation in mannose-binding proteins. 992 Sep 5
