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Structural determinants of APOBEC3B non-catalytic domain for molecular assembly and catalytic regulation

Structural determinants of APOBEC3B non-catalytic domain for molecular assembly and catalytic regulationThe catalytic activity of human cytidine deaminase APOBEC3B (A3B) has been correlated with kataegic mutational patterns within multiple cancer types. The molecular basis of how the N-terminal non-catalytic CD1 regulates the catalytic activity and consequently, biological function of A3B remains relatively unknown. Here, we report the crystal structure of a soluble human A3B-CD1 variant and delineate several structural elements of CD1 involved in molecular assembly, nucleic acid interactions and catalytic regulation of A3B. We show that (i) A3B expressed in human cells exists in hypoactive high-molecular-weight (HMW) complexes, which can be activated without apparent dissociation into low-molecular-weight (LMW) species after RNase A treatment. (ii) Multiple surface hydrophobic residues of CD1 mediate the HMW complex assembly and affect the catalytic activity, including one tryptophan residue W127 that likely acts through regulating nucleic acid binding. (iii) One of the highly positively charged surfaces on CD1 is involved in RNA-dependent attenuation of A3B catalysis. (iv) Surface hydrophobic residues of CD1 are involved in heterogeneous nuclear ribonucleoproteins (hnRNPs) binding to A3B. The structural and biochemical insights described here suggest that unique structural features on CD1 regulate the molecular assembly and catalytic activity of A3B through distinct mechanisms.

Nucleic Acids Res. 2017 Jul 7;45(12):7494-7506.
doi: 10.1093/nar/gkx362.

 

© 2017 Oxford University Press.

  Xiao X, Yang H, Arutiunian V, Fang Y, Besse G, Morimoto C, Zirkle B, Chen XS.

Another SBC Highlight:

Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex

Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex

 

 

Elife. 2017 May 24;6. pii: e27322.
doi: 10.7554/eLife.27322.

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Current Beamline Statistics:

APS PDB Depositions from BioSync
SBC Sector 19 2015 2016 2017 TOTAL
ID BM ID BM ID BM
PDB Depositions 259 32 227 29 153 27 5169

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Publications Total
SBC-CAT Publication List: 19-ID 1554
SBC-CAT Publication List: 19-BM 542
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APS Publications Database

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