The NHL repeat, named after ncl-1, HT2A and lin-41, is an amino acid sequence found largely in a large number of eukaryotic and prokaryoticproteins. For example, the repeat is found in a variety of enzymes of the copper type II, ascorbate-dependent monooxygenase family which catalyse the C-terminus alpha-amidation of biological peptides.[2] In many it occurs in tandem arrays, for example in the RING finger beta-box, coiled-coil (RBCC) eukaryotic growth regulators.[3] The arthropod 'Brain Tumor' protein (Brat; Q8MQJ9) is one such growth regulator that contains a 6-bladed NHL-repeat beta-propeller.[1][4]
The NHL repeats are also found in serine/threonine protein kinase (STPK) in diverse range of pathogenic bacteria. These STPK are transmembrane receptors with an intracellular N-terminal kinase domain and extracellular C-terminal sensor domain. In the STPK, PknD, from Mycobacterium tuberculosis, the sensor domain forms a rigid, six-bladed b-propeller composed of NHL repeats with a flexible tether to the transmembrane domain.
The NHL repeat has also been used to design a family of fully symmetrical 6-blade beta-propeller proteins called "Pizza".[5] These proteins can also be engineered to bind mineral nanocrystals.[6]
^Slack FJ, Ruvkun G (December 1998). "A novel repeat domain that is often associated with RING finger and B-box motifs". Trends Biochem. Sci. 23 (12): 474–5. doi:10.1016/S0968-0004(98)01299-7. PMID9868369.
^Voet, AR; Noguchi, H; Addy, C; Zhang, KY; Tame, JR (17 August 2015). "Biomineralization of a Cadmium Chloride Nanocrystal by a Designed Symmetrical Protein". Angewandte Chemie International Edition. 54 (34): 9857–60. doi:10.1002/anie.201503575. PMID26136355.
