Structure and functions of the interaction domains of C1r and C1s: keystones of the architecture of the C1 complex.
C1r and C1s, the proteases responsible for activation and proteolytic activity of the C1 complex of complement, share similar overall structural organizations featuring five nonenzymic protein modules (two CUB modules surrounding a single EGF module, and a pair of CCP modules) followed by a serine protease domain. Besides highly specific proteolytic activities, both proteases exhibit interaction properties associated with their N-terminal regions. These properties include the ability to bind Ca2+ ions with high affinity, to associate with each other within a Ca2+-dependent C1s-C1r-C1r-C1s tetramer, and to interact with C1q upon C1 assembly. Precise functional mapping of these regions has been achieved recently, allowing identification of the domains responsible for these interactions, and providing a comprehensive picture of their structure and function. The objective of this article is to provide a detailed and up-to-date overview of the information available on these domains, which are keystones of the assembly of C1, and appear to play an essential role at the interface between the recognition function of C1 and its proteolytic activity.
Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale Jean-Pierre Ebel(CEA-CNRS), Grenoble, France.
N M
NM
Thielens
B
B
Bersch
J F
JF
Hernandez
G J
GJ
Arlaud
D015923:Complement C1r / Q000737:chemistry / Q000502:physiology*; D003173:Complement C1s / Q000737:chemistry / Q000502:physiology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D015923:Complement C1r; D003173:Complement C1s