A nuclear localization signal at the SAM-SAM domain interface of AIDA-1 suggests a requirement for domain uncoupling prior to nuclear import.
The neuronal scaffolding protein AIDA-1 is believed to act as a convener of signals arising at postsynaptic densities. Among the readily identifiable domains in AIDA-1, two closely juxtaposed sterile alpha motif (SAM) domains and a phosphotyrosine binding domain are located within the C-terminus of the longest splice variant and exclusively in four shorter splice variants. As a first step towards understanding the possible emergent properties arising from this assembly of ligand binding domains, we have used NMR methods to solve the first structure of a SAM domain tandem. Separated by a 15-aa linker, the two SAM domains are fused in a head-to-tail orientation that has been observed in other hetero- and homotypic SAM domain structures. The basic nuclear import signal for AIDA-1 is buried at the interface between the two SAM domains. An observed disparity between the thermal stabilities of the two SAM domains suggests a mechanism whereby the second SAM domain decouples from the first SAM domain to facilitate translocation of AIDA-1 to the nucleus.
Kurabi
Arwa
A
Department of Biology, York University, Toronto, Ontario, Canada.
Brener
Stacey
S
Mobli
Mehdi
M
Kwan
Jamie J
JJ
Donaldson
Logan W
LW
D021581:Active Transport, Cell Nucleus; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008958:Models, Molecular; D019913:Nuclear Localization Signals; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary
C489945:ANKS1B protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019913:Nuclear Localization Signals