PMID- 10531307
OWN - NLM
STAT- MEDLINE
DCOM- 19991216
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 44
DP  - 1999 Oct 29
TI  - Decay accelerating activity of complement receptor type 1 (CD35). Two active
      sites are required for dissociating C5 convertases.
PG  - 31160-8
AB  - The goal of this study was to identify the site(s) in CR1 that mediate the
      dissociation of the C3 and C5 convertases. To that end, truncated derivatives of 
      CR1 whose extracellular part is composed of 30 tandem repeating modules, termed
      complement control protein repeats (CCPs), were generated. Site 1 (CCPs 1-3)
      alone mediated the decay acceleration of the classical and alternative pathway C3
      convertases. Site 2 (CCPs 8-10 or the nearly identical CCPs 15-17) had one-fifth 
      the activity of site 1. In contrast, for the C5 convertase, site 1 had only 0.5% 
      of the decay accelerating activity, while site 2 had no detectable activity.
      Efficient C5 decay accelerating activity was detected in recombinants that
      carried both site 1 and site 2. The activity was reduced if the intervening
      repeats between site 1 and site 2 were deleted. The results indicate that, for
      the C5 convertases, decay accelerating activity is mediated primarily by site 1. 
      A properly spaced site 2 has an important auxiliary role, which may involve its
      C3b binding capacity. Moreover, using homologous substitution mutagenesis,
      residues important in site 1 for dissociating activity were identified. Based on 
      these results, we generated proteins one-fourth the size of CR1 but with enhanced
      decay accelerating activity for the C3 convertases.
FAU - Krych-Goldberg, M
AU  - Krych-Goldberg M
AD  - Division of Rheumatology, Department of Medicine, Washington University School of
      Medicine, St. Louis, Missouri 63110, USA.
FAU - Hauhart, R E
AU  - Hauhart RE
FAU - Subramanian, V B
AU  - Subramanian VB
FAU - Yurcisin, B M 2nd
AU  - Yurcisin BM 2nd
FAU - Crimmins, D L
AU  - Crimmins DL
FAU - Hourcade, D E
AU  - Hourcade DE
FAU - Atkinson, J P
AU  - Atkinson JP
LA  - eng
GR  - R01 AI41592/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Complement 3b)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.4.21.- (Complement C3-C5 Convertases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Complement Activation/*physiology
MH  - Complement C3-C5 Convertases/*metabolism
MH  - Complement Pathway, Alternative/physiology
MH  - Complement Pathway, Classical/physiology
MH  - Conserved Sequence
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Peptide Fragments/genetics/metabolism
MH  - Receptors, Complement 3b/genetics/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Repetitive Sequences, Amino Acid
EDAT- 1999/10/26 09:00
MHDA- 2001/03/28 10:01
CRDT- 1999/10/26 09:00
PHST- 1999/10/26 09:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/10/26 09:00 [entrez]
AID - 10.1074/jbc.274.44.31160 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 29;274(44):31160-8. doi: 10.1074/jbc.274.44.31160.