Figure 4

Alignment of ROCO Domain Sequences. ROCO domain sequences were identified and aligned as detailed in Methods. The alignment presents the sequences of six ROCO domain reference proteins: "Ct_ROCO" (Chlorobium tepidum); "Ns_LRRP1" (Nostoc sp. PCC 7120); "Mb_ROCO1" (Methanosarcina barkeri str. Fusaro); "Hs_LRK1" (Homo sapiens); "Hs_LRRK2" (Homo sapiens); and "Ce_LRK1" (Caenorhabditis elegans). Most of the other sequences are designated by an organism prefix, followed by a number from the appropriate organism-specific protein database. Several Dictyostelium ("Dd") sequences are referred to by their gene names. Further information about the reference and candidate ROCO sequences, including organism prefixes and database accession numbers, are provided in Additional File 6. Conserved residues shown by Gotthardt et al. [15] as being critical to the functioning of both the bacterial protein and the human ROCO protein homologue LRRK2 are marked with blue lettering outlining and blue arrows. These positions are as follows: "T484" (our T53); "L487" (our L61); "G518" (our G110); and "Y804" (our Y642). Above the alignment is shown in red the secondary structure of the solved structure of the ROCO domain of Chlorobium tepidum (PDB: 3dpu_A). "A" indicates alpha helix, "B" indicates beta strand, and arrowhead symbols ("<" and ">") denote the beginning and ending of secondary structure regions. The functionally important "Switch I" ("SW1") and "Switch II" ("SW2") regions are indicated. Areas with "+++" symbols in purple represent poorly aligned sequence regions which have been edited from the alignment. The initial sequence region (positions 1-365) represents the ROC domain. The beginning of the COR domain is indicated.