Fc2 contributed two parallelb-strands each,
extending the bottom and top sheets, respec-
tively, of the twisted JCb-sandwich (Fig. 4A).
Despite its small size, the JC created an extensive,
~3600-Å^2 interface with the Fcs in the dimer,
underscoring its apropos title of“joining”chain.
Mechanism of IgA oligomerization
The JC-stabilized dimer core acted as a build-
ing block for larger polymers, consistent with
previous studies showing dissociation of tetra-
meric IgA into a JC-containing dimer and two
monomers upon mild reduction ( 4 ). In the
tetramer, an additional set of two parallel
b-strands, originating from the Fc3 and Fc4
tailpieces, continued the extension of the
twistedb-sandwich, with Fc3 adding to the
bottom sheet and Fc4 to the top (Fig. 4B).
However, in the pentamer, theb-sheet exten-
sion continued, with Fc5 adding one tailpiece
as a parallel strand to the top sheet and the
other tailpiece as a parallel strand to the bot-
tom sheet to cap theb-sandwich (Fig. 4C). Fc–
Fc contacts occurred at the Ca 2 – Ca3interface
in both the tetramer and pentamer using resi-
dues similarly involved in JCb-hairpin and
FcaRI binding (Fig. 4D and fig. S7). The
arrangement of Fc tailpieces into the JCb-
sandwich resulted in a striking repetitive
pattern of equivalent residues packed at the
core of pIgA, running parallel within each
b-sheet and antiparallel within theb-sandwich
(Fig.4,EtoG).Inthisarrangement,polarres-
idues were solvent exposed, whereas hydro-
phobic residues were buried at theb-sandwich
interface (Fig. 4, E to G). Thus, we propose a
model for IgA oligomerization in which the JC
acts as a template for the incorporation of IgAmonomers via their tailpieces. This creates a
molecularzipperofhydrophobicsidechains,
which stabilizes the polymer (Fig. 4G).Structure of the SC and interaction with pIgA
The SC comprises five Ig-like domains, of
which D1 is both necessary and sufficient for
pIgA binding, whereas D2 to D5 provide af-
finity enhancement ( 14 , 15 ). Previous struc-
tural analysis of the SC showed that in the
absence of pIgA, the SC adopts a closed con-
formation stabilized by the interaction among
D1, D4, and D5 (fig. S8A) ( 15 ). Our structures
revealed that the SC underwent a large
conformational change and interacted through
domains D1 and D5 with both Fcs of the IgA
dimercoreandtheJC(Fig.5Aandfig.S8A).The
asymmetry imparted by the JC allowed one-
to-one binding of the asymmetric SC to theKumaret al.,Science 367 , 1008–1014 (2020) 28 February 2020 3of7
Fig. 3. Structure of the JC.(A) Top, front, and bottom views of dimeric IgA1
with the JC colored rainbow from the N terminus (blue; model starts at residue
5) to the C terminus (red). The SC is omitted for clarity. (B) Topology diagram of
the JC with both intramolecular and intermolecular disulfide bonds shown.
(C) Magnified views of box c in (A) showing JC intramolecular (left) and
intermolecular (right) disulfide bonds. (D) Magnified views ofb-hairpins
1, 2, and 3 from boxes a, b, and d, respectively, in (A) and the interactions
they make with the Fcs.RESEARCH | RESEARCH ARTICLE