Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8575-E8584. doi: 10.1073/pnas.1701797114. Epub 2017 Sep 27.

A peptide extension dictates IgM assembly.

Author information

1
Center for Integrated Protein Science Munich at the Department Chemie, Technische Universität München, 85748 Garching, Germany.
2
Division of Genetics and Cell Biology, Università Vita-Salute IRCCS Ospedale San Raffaele, 20132 Milano, Italy.
3
Fakultät Chemie, Institut für Biologische Chemie, Universität Wien, 1090 Wien, Austria.
4
Division of Genetics and Cell Biology, Università Vita-Salute IRCCS Ospedale San Raffaele, 20132 Milano, Italy; sitia.roberto@hsr.it johannes.buchner@tum.de.
5
Center for Integrated Protein Science Munich at the Department Chemie, Technische Universität München, 85748 Garching, Germany; sitia.roberto@hsr.it johannes.buchner@tum.de.

Abstract

Professional secretory cells can produce large amounts of high-quality complex molecules, including IgM antibodies. Owing to their multivalency, polymeric IgM antibodies provide an efficient first-line of defense against pathogens. To decipher the mechanisms of IgM assembly, we investigated its biosynthesis in living cells and faithfully reconstituted the underlying processes in vitro. We find that a conserved peptide extension at the C-terminal end of the IgM heavy (Ig-μ) chains, termed the tailpiece, is necessary and sufficient to establish the correct geometry. Alanine scanning revealed that hydrophobic amino acids in the first half of the tailpiece contain essential information for generating the correct topology. Assembly is triggered by the formation of a disulfide bond linking two tailpieces. This induces conformational changes in the tailpiece and the adjacent domain, which drive further polymerization. Thus, the biogenesis of large and topologically challenging IgM complexes is dictated by a local conformational switch in a peptide extension.

KEYWORDS:

IgM structure; antibody; disulfide bond linkage; immunoglobulin fold; protein complex assembly

PMID:
28973899
PMCID:
PMC5642677
DOI:
10.1073/pnas.1701797114
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center