Mapping the Active Site of CD59

Yu, Jinghua; Abagyan, Ruben; Dong, Shanghong; Gilbert, Alexander; Nussenzweig, Victor; Tomlinson, Stephen

doi:10.1084/jem.185.4.745

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Article| February 17 1997

Mapping the Active Site of CD59

Jinghua Yu,

Jinghua Yu

From the *Department of Pathology, New York University Medical Center, New York 10016 and ‡Department of Biochemistry, The Skirball Institute, New York 10016

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Ruben Abagyan,

Ruben Abagyan

From the *Department of Pathology, New York University Medical Center, New York 10016 and ‡Department of Biochemistry, The Skirball Institute, New York 10016

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Shanghong Dong,

Shanghong Dong

From the *Department of Pathology, New York University Medical Center, New York 10016 and ‡Department of Biochemistry, The Skirball Institute, New York 10016

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Alexander Gilbert,

Alexander Gilbert

From the *Department of Pathology, New York University Medical Center, New York 10016 and ‡Department of Biochemistry, The Skirball Institute, New York 10016

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Victor Nussenzweig,

Victor Nussenzweig

From the *Department of Pathology, New York University Medical Center, New York 10016 and ‡Department of Biochemistry, The Skirball Institute, New York 10016

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Stephen Tomlinson

From the *Department of Pathology, New York University Medical Center, New York 10016 and ‡Department of Biochemistry, The Skirball Institute, New York 10016

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Author and Article Information

Jinghua Yu

From the *Department of Pathology, New York University Medical Center, New York 10016 and ‡Department of Biochemistry, The Skirball Institute, New York 10016

Ruben Abagyan

From the *Department of Pathology, New York University Medical Center, New York 10016 and ‡Department of Biochemistry, The Skirball Institute, New York 10016

Shanghong Dong

From the *Department of Pathology, New York University Medical Center, New York 10016 and ‡Department of Biochemistry, The Skirball Institute, New York 10016

Alexander Gilbert

From the *Department of Pathology, New York University Medical Center, New York 10016 and ‡Department of Biochemistry, The Skirball Institute, New York 10016

Victor Nussenzweig

From the *Department of Pathology, New York University Medical Center, New York 10016 and ‡Department of Biochemistry, The Skirball Institute, New York 10016

Stephen Tomlinson

From the *Department of Pathology, New York University Medical Center, New York 10016 and ‡Department of Biochemistry, The Skirball Institute, New York 10016

Address correspondence to Stephen Tomlinson, New York University Medical Center, Department of Pathology, MSB 127, 550 First Ave., New York, NY 10016. Dr. Dong's present address is Ohio State University, Department of Molecular Genetics, Biological Science Building, 484 West 12th St., Columbus, OH 43210.

¹Abbreviations used in this paper: CHO, Chinese hamster ovary cells; GPI, glycosylphosphatidylinositol; MAC, membrane attack complex; NHS, normal human serum.

Received: July 08 1996

Revision Received: November 27 1996

Online ISSN: 1540-9538

Print ISSN: 0022-1007

1997

J Exp Med (1997) 185 (4): 745–754.

https://doi.org/10.1084/jem.185.4.745

CD59 is a widely distributed membrane-bound inhibitor of the cytolytic membrane attack complex (MAC) of complement. This small (77 amino acid) glycoprotein is a member of the Ly6 superfamily of proteins and is important in protecting host cells from the lytic and proinflammatory activity of the MAC. CD59 functions by binding to C8 and/or C9 in the nascent MAC and interfering with C9 membrane insertion and polymerization. We present data obtained from a combination of molecular modeling and mutagenesis techniques, which together indicate that the active site of CD59 is located in the vicinity of a hydrophobic groove on the face of the molecule opposite to a “hydrophobic strip” suggested earlier. In addition, removal of the single N-linked glycosylation site at Asn18 of CD59 resulted in an enhancement of complement inhibitory activity.

1997

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