Science 28Feb2020

dimer. The interaction with D1 was noncovalent
and involved all three complementarity deter-
mining region (CDR)–like loops, whereas the
interaction with D5 was mediated by a single
disulfide bond (Fig. 5). Although D2 to D4 did
not make direct contacts with pIgA, they pro-
vided the correct spacing to allow the inter-
actions of D1 and D5 with the dimer. D2 to
D5 were arranged in a head-to-tail manner,
whereas a sharp 180° turn in the D1–D2 linker
allowed D1 to position its three CDRs to bind

pIgA (Fig. 5A). The described kinked SC con-

formation was stabilized via an aromatic-rich

D1–D3 interface (Fig. 5A). Approximately one-

third of the ~1055 Å^2 of D1 buried surface area

resulted from interactions with the JC C ter-

minus, consistent withthe requirement of the

JC for pIgR binding and transcytosis ( 16 ).

Discussion

This work presents the first atomic-level res-

olution structures of pIgA bound to the elusive

JC and sheds light on the mechanism involved

in higher-order polymer formation. It also

presents for the first time the architecture of

sIgA and describes at the atomic level the

molecular basis for recognition of pIgA by

the SC of the pIgR. Our structures show that

upon pIgA binding, the SC undergoes a large

conformational change. In the closed SC con-

formation, the majority of the Fc1-binding D1

residues are at the D1–D4–D5 interface and at

least partially buried, whereas the JC and Fc2

Kumaret al.,Science 367 , 1008–1014 (2020) 28 February 2020 5of7

Fig. 5. Recognition of pIgA by the SC.(A) sIgA1 dimer with IgA shown as a
transparent surface withcartoon representations underneath. Domains D1 to
D5 of the SC are color coded as indicated with D1 CDR1, CDR2, and CDR3
highlighted in green. Magnification of the aromatic-rich D1–D3 interface
shown in the inset. (B) Interaction of SC D5 and Fc2 with inset magnifying the
D5C468–Fc2C311disulfide bond. (C) Relative positioning of D1 CDR1 (box a),

CDR2 (box b), and CDR3 (box c) and their interactions with pIgA. Domains D2

to D5 are omitted for clarity. (D) Magnification of box a from (C) to show

D1 CDR1 interactions with Fc1 and JC. Side chains are shown as sticks and

polar interactions as dashed yellow lines. (E) Magnification of box b from (C)

showing interactions among D1 CDR1, CDR2, CDR3, and Fc1. (F)Magnification

of box c from (C) showing interactions among D1 CDR3, Fc1, Fc2, and JC.

RESEARCH | RESEARCH ARTICLE