C1q and its growing family

Clq is the target recognition protein of the classical complement pathway and a major connecting link between innate and acquired immunity. As a charge pattern recognition molecule of innate immunity, Clq can engage a broad range of self and non-self ligands via its heterotrimeric globular (gClq) domain and thus trigger the classical pathway. The trimeric gClq signature domain has been identified in a variety of non-complement proteins that can be grouped together as a Clq family. The X-ray crystal structures of the gClq domain of a few members of the Clq family reveal a compact jelly-roll P-sandwich fold similar to that of the multifunctional tumor necrosis factor (TNF) ligand family, hence the Clq and TNF superfamily. This review is an update on the structural and functional aspects of the gClq domain of human Clq. We also mention the diverse range of proteins that utilize a gClq domain in order to reflect on its importance as a versatile scaffold to support a variety of functions. (c) 2006 Elsevier GmbH. All rights reserved.