Identification of a complement receptor 1 peptide for inhibition of immune hemolysis.
Complement sensitization of red blood cells (RBCs) can cause life-threatening hemolytic anemias. We have previously shown that complement receptor 1 (CR1) derivatives specifically the N-terminal region with decay accelerating activity (DAA) for inactivation of a key enzyme in the complement cascade can reduce complement-mediated RBC destruction in vitro and in an in vivo mouse model of hemolytic transfusion reaction. In the present study, we have modeled the N-terminal CR1 molecule based on the X-ray crystal structure of decay accelerating factor and the NMR structure of a homologous CR1 domain. Based on the homology model, we identified a 34-mer peptide encompassing the putative DAA which in vitro reduced hemolysis, C3a release and surface C3 deposition. More importantly, this peptide at 0.6 mM was effective in prolonging survival of transfused incompatible RBCs in vivo. Our results indicate that CR1-based structure-function studies may provide insights for developing structure-derived transfusion therapeutics in the future.
Yu
Jin
J
Laboratory of Complement Biology, New York Blood Center, 310, E 67th Street, New York, NY 10021, USA.
Heck
Susanne
S
Flow Cytometry Laboratory, New York Blood Center, New York, USA.
Debnath
Asim
A
Laboratory of Molecular Modeling, New York Blood Center, New York, USA.
Yazdanbakhsh
Karina
K
Laboratory of Complement Biology, New York Blood Center, 310, E 67th Street, New York, NY 10021, USA.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D006461:Hemolysis / Q000276:immunology*; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000276:immunology*; D011485:Protein Binding; D011487:Protein Conformation; D011951:Receptors, Complement / Q000737:chemistry / Q000276:immunology; D017463:Receptors, Complement 3b / Q000737:chemistry* / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
D010455:Peptides; D011951:Receptors, Complement; D017463:Receptors, Complement 3b