The dependence of Ig class-switching on the nuclear export sequence of AID likely reflects interaction with factors additional to Crm1 exportin.
Activation-induced deaminase (AID) is a B lymphocyte-specific DNA deaminase that triggers Ig class-switch recombination (CSR) and somatic hypermutation. It shuttles between cytoplasm and nucleus, containing a nuclear export sequence (NES) at its carboxyterminus. Intriguingly, the precise nature of this NES is critical to AID's function in CSR, though not in somatic hypermutation. Many alterations to the NES, while preserving its nuclear export function, destroy CSR ability. We have previously speculated that AID's ability to potentiate CSR may critically depend on the affinity of interaction between its NES and Crm1 exportin. Here, however, by comparing multiple AID NES mutants, we find that - beyond a requirement for threshold Crm1 binding - there is little correlation between CSR and Crm1 binding affinity. The results suggest that CSR, as well as the stabilisation of AID, depend on an interaction between the AID C-terminal decapeptide and factor(s) additional to Crm1.
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, UK.
Julia I
JI
Ellyard
Amelie S
AS
Benk
Benjamin
B
Taylor
Cristina
C
Rada
Michael S
MS
Neuberger
D019943:Amino Acid Substitution / Q000502:physiology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D004795:Enzyme Stability / Q000502:physiology; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000502:physiology*; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D049790:Nuclear Export Signals / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000097606:Exportin 1 Protein; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D003564:Cytidine Deaminase; D028884:Karyopherins; D049790:Nuclear Export Signals; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D000097606:Exportin 1 Protein; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
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