section 35.10
Complement
829
TABLE 35-3
Proteins o f the Complement System (
c o n tin u e d )
CLASSICAL
PATHWAY
Initiated by IgGl, IgG2, IgG3 or IgM—antigen complexes
Protein/Subunit(s)
Serum Cone.
Molecular
Weight
Description and Role of the
Active Form
(mg/L)
(chains)
Active Forms in These Pathways
C l (multi-subunit)
Clq
83-125
460,000
Requires Ca2+ for subunit association
Shaped like a tulip with a “stalk” that contains
Clr
34-48
(6Ax 26,500)
(6B x 26,500)
(6C x 24,000)
83,000
collagen-like domains and “petals”, globular domains.
G lo b u la r d o m a in s b in d F c re g io n s o f l g G a n d Ig M
a n tig e n -a n tib o d y c o m p le x e s, le a d in g to a c tiv a tio n
o f C l r a n d in itia tio n o f th e c la s s ic a l p a th w a y .
Proenzyme to serine protease; auto-activates and
After activation
(a,
-56,000)
activates Cls. Activated C lr consists of two
becomes 2 chains
(/3 -27,000)
polypeptide chains, C lra, C1
r/3. Anaphylatoxin
Cls
34
85,000
activity (Clra), active site-containing chain (Clr/3)
Proenzyme to serine protease; activates C2 and C4 to
After activation
(a, -56,000)
produce C4b and C2a which form the C4b2a
becomes 2 chains
(/3 -27,000)
(C3 convertase) that activates C3. Activated Cls
C4 (before activation)
350-600
204,000
consists of two chains, C lsa and Cls/3.
C4a
C4b
C2
25
110,000
Amino terminal residues, anaphylatoxin (weak),
increases vascular permeability and causes mast
cell degranulation
C4b contains a thioester bond that can attach C4b can
attach covalently to target cells. Forms a complex
with C2, allowing Cls to cleave C2
Contains serine protease active site of C4b2a, which
C2a
C3 Convertase (C4b2a)
C3 (See alternative
1,110-1,710
185,000
can cleave C3 and C5
Component of C3 convertase
Activates C3, i.e. is the classical pathway C3
convertase
Precursor to C3a and C3b
pathway also)
C3a
C3b
Anaphylatoxin, increases vascular permeability and
causes mast cell degranulation
C3b can attach covalently to target cells via reaction
with the C3 thioester. Opsonin
(c o n tin u e d )
