Role of the cystine-knot motif at the C-terminus of rat mucin protein Muc2 in dimer formation and secretion.

Role of the cystine-knot motif at the C-terminus of rat mucin protein Muc2 in dimer formation and secretion. Research Abstract Details 

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Role of the cystine-knot motif at the C-terminus of rat mucin protein Muc2 in dimer formation and secretion. Abstract Text:

S L Bell,G Xu,J F Forstner,

DNA constructs based on the 534-amino-acid C-terminus of rat mucin protein Muc2 (RMC), were transfected into COS cells and the resultant (35)S-labelled dimers and monomers were detected by SDS/PAGE of immunoprecipitates. The cystine-knot construct, encoding the C-terminal 115 amino acids, appeared in cell lysates as a 45 kDa dimer, but was not secreted. A construct, devoid of the cystine knot, failed to form dimers. Site-specific mutagenesis within the cystine knot was performed on a conserved unpaired cysteine (designated Cys-X), which has been implicated in some cystine-knot-containing growth factors as being important for intermolecular disulphide-bond formation. Dimerization of RMC was effectively abolished. Each cysteine (Cys-1-Cys-6) comprising the three intramolecular disulphide bonds of the cystine knot was then mutated. Dimer formation was impaired in each case, although much less so for the Cys-3 mutant than the others. Abnormal high-molecular-mass, disulphide-dependent aggregates formed with mutations Cys-1, Cys-2, Cys-4 and Cys-5(,) and were poorly secreted. It is concluded that the intact cystine-knot domain is essential for dimerization of the C-terminal domain of rat Muc2, and that residue Cys-X in the knot plays a key role. The structural integrity of the cystine knot, maintained by intramolecular bonds Cys-1-Cys-4, Cys-2-Cys-5 and Cys-3-Cys-6, also appears to be important for dimerization, probably by allowing correct positioning of the unpaired Cys-X residue for stable intermolecular cystine-bond formation.

Role of the cystine-knot motif at the C-terminus of rat mucin protein Muc2 in dimer formation and secretion. Publishing Authors By Initials

SL Bell,G Xu,JF Forstner,

For similar amino acids, peptides, and proteins: amino acids: amino acids, neutral: serine research abstracts see: amino acids, peptides, and proteins: amino acids: amino acids, neutral: serine research

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Role of the cystine-knot motif at the C-terminus of rat mucin protein Muc2 in dimer formation and secretion. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Biochemical journal

VOLUME: 357

Page Numbers: 203-9

Journal Abbreviation: Biochem. J.

ISSN: 0264-6021

DAY: 1

MONTH: Jul

YEAR: 2001

Role of the cystine-knot motif at the C-terminus of rat mucin protein Muc2 in dimer formation and secretion. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984726

Role of the cystine-knot motif at the C-terminus of rat mucin protein Muc2 in dimer formation and secretion. Keywords Mesh Terms:

KEYWORDS: Serine

MESH TERMS: metabolism

Chemical & Substance for Abstract: Role of the cystine-knot motif at the C-terminus of rat mucin protein Muc2 in dimer formation and secretion. Information

Substance Name: Cystine

Registry Number: 56-89-3

Grant and Affiliation Information for Role of the cystine-knot motif at the C-terminus of rat mucin protein Muc2 in dimer formation and secretion.

AFFILIATION: Division of Structural Biology and Biochemistry, Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.

Country: England

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MEDLINETA: Biochem J

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