Clara cell 10 kDa protein (CC10): Comparison of structure and function to uterogloblin

Gurmukh Singh, Sikandar L. Katyal, William E. Brown, Amy L. Kennedy, Ushasi Singh, Mari Lou Wong-Chong

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

The cellular localization, functional activities and structure of rat and human Clara cell 10 kDa proteins (CC10) are compared to rabbit uteroglobin. CC10 is present exclusively in the non-ciliated cells of the surface epithelium of the pulmonary airways, whereas uteroglobin is reported to be present in the lung and reproducted organs. There is about 55% identity between the amino acid sequences of rat CC10 and either rabbit uteroglobin or human CC10. The latter two have 61% identity. Using the known structure of uteroglobin as the model, correclations between the structure and function for this group of proteins are made. Substitution of the residues for the rat and human CC10 into the structure of uteroglobin suggests that these proteins may be members of a structurally homologous family. Some of the functional differences may be due to distortion of the hydrophobic pocket in the dimeric protein and a surface hypervariability located on one contiguous helix and β turn. Rat CC10 and rabbit uteroglobin both, nearly equally, inhibit papain and bind progesterone. Human CC10 does not inhibit papain and has markedly lower progesterone binding (4.6% of rabbit uteroglobin). Antiinflammatory activity of synthetic peptides corresponding to a homologous sequence region of uteroglobin and the two Clara cell proteins was tested. The region chosen has sequence similarity to lipoeortin I. The peptides not only failed to inhibit carrageenan-induced foot pad swelling but exacerbated it. All three proteins inhibit pancreatic phospholipase A2. The phospholipase A2 inhibitory effect of the CC10 may be important in regulating the inflammatory responses in the lung.

Original languageEnglish (US)
Pages (from-to)348-355
Number of pages8
JournalBiochimica et Biophysica Acta (BBA)/Protein Structure and Molecular
Volume1039
Issue number3
DOIs
StatePublished - Jul 6 1990
Externally publishedYes

Keywords

  • Clara cell 10 kDa protein
  • Immunohistochemistry
  • Phospholipase A inhibitor
  • Progestone Antiinflammatory activity
  • Proteinase inhibitor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology

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