HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wallis, R. Search for Related Content PubMed PubMed Citation Articles by Wallis, R.

Dominant Effects of Mutations in the Collagenous Domain of Mannose-Binding Protein¹

Department of Biochemistry, Glycobiology Institute, University of Oxford, Oxford, United Kingdom

Individuals heterozygous for mutant alleles encoding serum mannose-binding protein (MBP, also known as mannose-binding lectin) show increased susceptibility to infections caused by a wide range of pathogenic microorganisms. To investigate the molecular defects associated with heterozygosity, wild-type rat serum MBP polypeptides (MBP-A: 56% identical in sequence to human MBP) and rat MBP polypeptides containing mutations associated with human immunodeficiency have been coexpressed using a well-characterized mammalian expression system. The resulting proteins are secreted almost exclusively as heterooligomers that are defective in activating the complement cascade. Functional defects are caused by structural changes to the N-terminal collagenous and cysteine-rich domains of MBP, disrupting interactions with associated serine proteases. The dominant effects of the mutations demonstrate how the presence of a single mutant allele gives rise to the molecular defects that lead to the disease phenotype in heterozygous individuals.

This article has been cited by other articles:

				N. Rawal, R. Rajagopalan, and V. P. Salvi Activation of Complement Component C5: COMPARISON OF C5 CONVERTASES OF THE LECTIN PATHWAY AND THE CLASSICAL PATHWAY OF COMPLEMENT J. Biol. Chem., March 21, 2008; 283(12): 7853 - 7863. [Abstract] [Full Text] [PDF]

				R. Wallis, N. J. Lynch, S. Roscher, K. B. Reid, and W. J. Schwaeble Decoupling of Carbohydrate Binding and MASP-2 Autoactivation in Variant Mannose-Binding Lectins Associated with Immunodeficiency J. Immunol., November 15, 2005; 175(10): 6846 - 6851. [Abstract] [Full Text] [PDF]

				A. Megia, L. Gallart, J.-M. Fernandez-Real, J. Vendrell, I. Simon, C. Gutierrez, and C. Richart Mannose-Binding Lectin Gene Polymorphisms Are Associated with Gestational Diabetes Mellitus J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5081 - 5087. [Abstract] [Full Text] [PDF]