Switches.ELM

Switch #:

SWTI000329

Switch type:
Specificity

Switch subtype:
Domain hiding

Description:
An intramolecular interaction between the importin beta-binding (IBB) domain and the NLS-binding pocket of Importin subunit alpha (SRP1) prevents binding of NLS cargo (e.g. Large T antigen) in the absence of Importin subunit beta-1 (KAP95) by hiding of the NLS-binding pocket. Binding of the IBB of Importin subunit alpha (SRP1) to Importin subunit beta-1 (KAP95) relieves this auto-inhibitory interaction and increases the affinity of Importin subunit alpha (SRP1) for NLS cargo.

Participants:
(1) Importin subunit alpha (SRP1)
(2) Large T antigen

Interactions

Interaction #1 SRP1 - SRP1(intramolecular)
intramolecular
Is mutually exclusive with Interaction #2 - SRP1

Interfaces
(1) TRG_NLS_Bipartite_1 motif (₄₄RKAKRDEALAKRRNF₅₈) in Importin subunit alpha (SRP1)
(2) Armadillo/beta-catenin-like repeat_(119-457) in Importin subunit alpha (SRP1)
Additional Information
Structural information: 1IAL

Interaction #2 - SRP1

Is mutually exclusive with Interaction #1 SRP1 - SRP1

Interfaces
(3) TRG_NLS_MonoExtN_4 motif (₁₂₆PKKKRKV₁₃₂) in Large T antigen
(4) Armadillo/beta-catenin-like repeat_(119-457) in Importin subunit alpha (SRP1)

Interaction Regulation
Effector binding Abrogation (Importin subunit alpha (SRP1)) of the Large T antigen TRG_NLS_MonoExtN_4 motif - Importin subunit alpha (SRP1) Armadillo/beta-catenin-like repeat interaction

Additional Information
Structural information: 1BK6

Context

References

(1) Characterization of the auto-inhibitory sequence within the N-terminal domain of importin alpha.
Harreman et al. J. Biol. Chem. (2003)