Room temperature structure of human IgG4-Fc from crystals analysed in situ.

ABSTRACT: The Fc region of IgG antibodies (C?2 and C?3 domains) is responsible for effector functions such as antibody-dependent cell-mediated cytotoxicity and phagocytosis, through engagement with Fc? receptors, although the ability to elicit these functions differs between the four human IgG subclasses. A key determinant of Fc? receptor interactions is the FG loop in the C?2 domain. High resolution cryogenic IgG4-Fc crystal structures have revealed a unique conformation for this loop, which could contribute to the particular biological properties of this subclass. To further explore the conformation of the IgG4 C?2 FG loop at near-physiological temperature, we solved a 2.7Å resolution room temperature structure of recombinant human IgG4-Fc from crystals analysed in situ. The C?2 FG loop in one chain differs from the cryogenic structure, and adopts the conserved conformation found in IgG1-Fc; however, this conformation participates in extensive crystal packing interactions. On the other hand, at room temperature, and free from any crystal packing interactions, the C?2 FG loop in the other chain adopts the conformation previously observed in the cryogenic IgG4-Fc structures, despite both conformations being accessible. The room temperature human IgG4-Fc structure thus provides a more complete and physiologically relevant description of the conformation of this functionally critical C?2 FG loop.

SUBMITTER: Davies AM 

PROVIDER: S-EPMC5226057 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature