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Mapping the Regions of the Complement Inhibitor CD59 Responsible for Its Species Selective Activity

Summary: Mapping the Regions of the Complement Inhibitor CD59 Responsible for Its
Species Selective Activity
Jinghua Yu, Shanghong Dong,, Neil K. Rushmere,| B. Paul Morgan,| Ruben Abagyan, and Stephen Tomlinson*,
Department of Pathology, New York UniVersity Medical Center, 550 First AVenue, and Department of Biochemistry,
The Skirball Institute, 540 First AVenue, New York, New York 10016, and Department of Medical Biochemistry,
UniVersity of Wales College of Medicine, Heath Park, Cardiff, U.K.
ReceiVed April 9, 1997; ReVised Manuscript ReceiVed May 22, 1997X
ABSTRACT: CD59 is a widely distributed membrane-bound glycoprotein that inhibits the formation of the
cytolytic membrane attack complex (MAC) of complement on host cells. CD59 from different species
varies in its capacity to inhibit heterologous complement, and this species selective function of CD59
contributes to the phenomenon of homologous restriction. Here, we demonstrate that human CD59 is
not an effective inhibitor of rat complement, although rat CD59 inhibits rat and human complement equally
well. By constructing human-rat CD59 chimeric proteins, we have mapped the residues important in
conferring human CD59 species selectivity to two regions; 40-47 and 47-66 in the primary structure.
Analysis of a model of the molecular surface of human CD59 revealed that residues 40-66 mapped to
a region in the three-dimensional structure that surrounds residues previously identified as important for
CD59 function.
Activation of complement results in the formation of C3/
C5 convertase enzymes on the activating surface. The
convertases serve to amplify the cascade and may lead to


Source: Abagyan, Ruben - School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego


Collections: Biology and Medicine