NHL repeat explained

Symbol:	NHL
NHL repeat
Pfam:	PF01436
Pfam Clan:	CL0186
Interpro:	IPR001258
Scop:	1q7f
Cdd:	cd05819
Pdb:	,,

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 prokaryotic proteins. 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.^[1] In many it occurs in tandem arrays, for example in the RING finger beta-box, coiled-coil (RBCC) eukaryotic growth regulators.^[2] The arthropod 'Brain Tumor' protein (Brat;) is one such growth regulator that contains a 6-bladed NHL-repeat beta-propeller.^[3]

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".^[4] These proteins can also be engineered to bind mineral nanocrystals.^[5]

Notes and References

1. Kano S, Miyajima N, Fukuda S, Hatakeyama S . Tripartite motif protein 32 facilitates cell growth and migration via degradation of Abl-interactor 2 . Cancer Res. . 68 . 14 . 5572–5580 . July 2008 . 18632609 . 10.1158/0008-5472.CAN-07-6231 . free .
2. Slack FJ, Ruvkun G . A novel repeat domain that is often associated with RING finger and B-box motifs . Trends Biochem. Sci. . 23 . 12 . 474–5 . December 1998 . 9868369 . 10.1016/S0968-0004(98)01299-7.
3. Edwards TA, Pyle SE, Wharton RP, Aggarwal AK . Structure of Pumilio reveals similarity between RNA and peptide binding motifs . Cell . 105 . 2 . 281–9 . April 2001 . 11336677 . 10.1016/S0092-8674(01)00318-X. 9341061 . free .
4. Tame . Jeremy R. H. . Zhang . Kam Y. J. . Park . Sam-Yong . Unzai . Satoru . Terada . Daiki . Simoncini . David . Addy . Christine . Noguchi . Hiroki . Voet . Arnout R. D. . Computational design of a self-assembling symmetrical β-propeller protein . Proceedings of the National Academy of Sciences . 21 October 2014 . 111 . 42 . 15102–15107 . 10.1073/pnas.1412768111 . 25288768 . en . 0027-8424. 4210308 . 2014PNAS..11115102V . free .
5. Voet . AR . Noguchi . H . Addy . C . Zhang . KY . Tame . JR . Biomineralization of a Cadmium Chloride Nanocrystal by a Designed Symmetrical Protein. . Angewandte Chemie International Edition. 17 August 2015 . 54 . 34 . 9857–60 . 10.1002/anie.201503575 . 26136355.