title: Structural features of antiviral DNA cytidine deaminases.
abstract: The APOBEC3 (A3) family of cytidine deaminases plays a vital role for innate defense against retroviruses. Lentiviruses such as HIV-1 evolved the Vif protein that triggers A3 protein degradation. There are seven A3 proteins, A3A-A3H, found in humans. All A3 proteins can deaminate cytidines to uridines in single-stranded DNA (ssDNA), generated during viral reverse transcription. A3 proteins have either one or two cytidine deaminase domains (CD). The CDs coordinate a zinc ion, and their amino acid specificity classifies the A3s into A3Z1, A3Z2, and A3Z3. A3 proteins occur as monomers, dimers, and large oligomeric complexes. Studies on the nature of A3 oligomerization, as well as the mode of interaction of A3s with RNA and ssDNA are partially controversial. High-resolution structures of the catalytic CD2 of A3G and A3F as well as of the single CD proteins A3A and A3C have been published recently. The NMR and X-ray crystal structures show globular proteins with six α-helices and five β sheets arranged in a characteristic motif (α1-β1-β2/2'-α2-β3-α3-β4-α4-β5-α5-α6). However, the detailed arrangement and extension of individual structure elements and their relevance for A3 complex formation and activity remains a matter of debate and will be highlighted in this review.
authors.forename: Ananda Ayyappan Jaguva
authors.initials: AA
authors.lastname: Vasudevan
authors.forename: Sander H J
authors.initials: SH
authors.lastname: Smits
authors.forename: Astrid
authors.initials: A
authors.lastname: Höppner
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Koenig
authors.forename: Carsten
authors.initials: C
authors.lastname: Münk
mesh_terms: D000071478:APOBEC Deaminases; D002384:Catalysis; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000737:chemistry* / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012190:Retroviridae / Q000201:enzymology / Q000378:metabolism; D053838:Scattering, Small Angle
chemical_list: D004277:DNA, Single-Stranded; D004279:DNA, Viral; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase