Comparative analyses of the TRIM NHLs. (a) Sequence alignment of the NHL motifs from all four human TRIMs within subfamily VII, the NHL-like domain of TRIM56 and the NHL domain of the homologue DrLIN41. The yellow boxes highlight the amino acids in the vicinity of the central groove of the top opening surface, while amino acids in red are the genetic mutations linked to diseases (see also Fig. 3). (b) A sequence-based phylogenetic tree for the NHL and NHL-like domains of human TRIMs and their homologue DrLIN41. Below are the sequence identities and r.m.s.d. calculated from structural comparison between the pairs. (c) Superimposition of the TRIM–NHL structures reveals highly conserved topology of the β-propeller architectures, yet slight differences are observed for some connecting loops (arrows). (d) Sequence conservation at the top opening among human TRIM NHLs calculated using ConSurf (Ashkenazy et al., 2016). (e) Mapping of amino acid compositions (top) and electrostatic potentials (bottom) of the central grooves at the top surface of TRIM2, TRIM3 and TRIM71 NHLs.