Science 28Feb2020

changes, leading to the formation of a very

different triangular shape (Fig. 4C). D4-D5 ro-

tates 120° en bloc to become co-linear with D2-

D3, and the newly formed D3-D4 interface buries

a large surface area (1486 Å^2 ). D1 is rotated 84°

and packs onto D2-D3. This large conforma-

tional change is consistent with a previous

double electron-electron resonance (DEER)

spectroscopy study ( 22 ). In particular, the dis-

tance between the Caatoms of D1-Thr^67 and

D5-Gln^491 is 78 Å in this new conformation,

in good agreement with DEER measurements

showing that ligand binding induces a sepa-

ration of these two residues beyond 70 Å. The

three CDRs function as a central hub to me-

diate a network of interactions with Fcm1, Fcm5,

and the J-chain (Fig. 4, A, D, and E, and fig.

S3,ItoN).InCDR1,pIgR/SCresidueVal^29 in-

teracts with J-chain residue Ala^132 in the

J-chain C-terminal hairpin (Fig. 4D). pIgR/SC

residue Asn^30 forms a hydrogen bond with

Liet al.,Science 367 , 1014–1017 (2020) 28 February 2020 3of4

AB

CDR2

CDR3

E53P

Y55P

R451Fcμ1A

R514Fcμ1A

E468Fcμ1B

N97P

L466Fcμ1B Y576 R99P

Fcμ5B

T574Fcμ5A

L101P

Y576Fcμ5A

P544Fcμ1A

E468Fcμ1B

Y576Fcμ5B

V29P

A132J

N30P

H32P

Y134J

R34P

CDR1

R105J

DE

F

Strep

pull-down

Input

SC-His

Strep-IgM-Fc

J chain-His

WT

• 
  


• 
  

+

+

+

+

+

+

WTV29N/R31SR99N/L101T

anti His (SC)

anti Strep

anti His (J)

anti His (SC)

anti Strep

anti His (J)

C

D5

D2

D3

D4

CDR1 CDR2

CDR3

T67

Q491

28 Å

D1

S T

D5

D2

D3

D4

CDR2 CDR1

CDR3

T67

Q491

78 Å

D1

A

Fcμ 1

Fcμ 5

J

CDR1

CDR2

CDR3

SC

D1

Fig. 4. Conformational change of pIgR/SC and its interaction with the
Fcm-J complex.(A) The three CDRs (magenta) in pIgR/SC-D1 (gold)
interact with Fcm1(blue),Fcm5 (cyan), and the J-chain (red). pIgR/SC is
shown as a surface representation. Its D2 to D5 domains are shown in
white. (B) The structure of apo pIgR/SC (PDB ID 5D4K). D1 is shown in gold,
with the three CDR loops highlighted in magenta. The Caatoms of D1-Thr^67

and D5-Gln^491 are shown as spheres, and the distance between them is

indicated. (C)ThestructureofpIgR/SCintheFcm-J-SC complex.

(D) Detailed view of the interactions at the D1-CDR1 region. Polar

interactions are indicated by dashed lines. (E) Detailed view of the

interactions at the CDR2 and CDR3 region. (F)SCmutantsdisplay

reduced interactions with Fcm-J.

ABA

β 1 C68J

β 2

β 4 β^3

C14J

C575Fcμ5B

Fcμ1A

Fcμ5B

N-wing

C-wing

Fcμ5A

Fcμ4B

Y134J

P130J

A127JT126J

V113J

L115J

P114J

F358

P544

V547

V124J

L359

F485

P494

M489

V537

C575Fcμ1A

C575Fcμ5A

C575Fcμ4B

Fig. 3. Structure of the J-chain and its interactions with Fcm.(A) The J-chain has a two-winged
structure and interacts with the tailpieces of the Fcmpentamer. (B) The C-terminal hairpin of the J-chain
interacts with Fcm1A.

RESEARCH | REPORT