Sites within the complement C3b/C4b receptor important for the specificity of ligand binding

Journal Article · Wed May 15 04:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.10.4353· OSTI ID:5934018

Krych, M; Hourcade, D; Atkinson, J P ^[1]

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1. Washington Univ. School of Medicine, St. Louis, MO (United States)

Cysteine-rich repeating units of 40-70 amino acids are building blocks of many mammalian proteins, including 12 proteins of the complement system. Human complement receptor type 1 (CR1) is composed of 30 such tandemly arranged motifs, designated short consensus repeats (SCRs), which constitute the entire extracellular portion of this protein. Klickstein et al. localized a C4b binding domain to SCR-1 and/or SCR-2 and a C3b binding domain to SCR-8 and/or SCR-9. These SCRs bind different ligands, although SCR-1 and SCR-8 are 55% homologous and SCR-2 and SCR-9 are 70% homologous. To examine if one or two SCRs are required for ligand binding and to define sites within the SCRs that determine specificity of binding, mutagenesis analysis of a truncated, secreted form of CR1 was done. The latter, composed of the first eight and one-half amino-terminal SCRs of CR1, efficiently bound C4b but not iC3. SCR-1 and SCR-2 were necessary for this interaction. Analysis of the mutant CR1-4 proteins, in which amino acids in SCR-1 and SCR-2 were substituted a few at a time with the homologous amino acids of SCR-8 and SCR-9, led to the identification of one amino acid in SCR-1 and three amino acids in SCR-2 important for C4b binding. These results provide identification of amino acids within SCRs that are important for ligand binding.

• OSTI ID: 5934018
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:10; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
AMINO ACIDS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
COMPLEMENT
CYSTEINE
DAYS LIVING RADIOISOTOPES
EVEN-ODD NUCLEI
ISOTOPES
LIGANDS
LIGHT NUCLEI
MEMBRANE PROTEINS
MOLECULAR STRUCTURE
MUTAGENESIS
MUTANTS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PROTEINS
RADIOISOTOPES
RECEPTORS
SULFUR 35
SULFUR ISOTOPES
THIOLS