Additional file 1: of ERK1 and ERK2 present functional redundancy in tetrapods despite higher evolution rate of ERK1
Creators: name: Buscà, Roser
name: Christen, Richard
name: Lovern, Matthew
name: Clifford, Alexander
name: Yue, Jia-Xing
name: Goss, Greg
name: Pouysségur, Jacques
name: Lenormand, Philippe
Publisher: name: Figshare
Year: 2015
Subjects: subject: Biophysics
subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Molecular Biology
subject: Neuroscience
subject: Physiology
subject: Evolutionary Biology
subject: Immunology
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: 111714 Mental Health
subject: FOS: Health sciences
subject: FOS: Health sciences
subject: 110309 Infectious Diseases
subject: 60506 Virology
subject: Computational Biology

description: A. Only one difference (ile/leu) between ERK1 and ERK2 among the 23 amino-acids putatively interacting with substrates. (i-ii) residues shown to be critical in co-crystal structures for substrate binding in mouse ERK2 are colored in blue. Residue differences in aligned mouse ERK1 and ERK2 sequences are shown or boxed in red. (i) Binding domains on ERKs for binding to the DEJL(KIM) motif of substrates (includes the common docking (CD) domain on ERK) [13]; upper sequences: hydrophobic groove of ERKs, lower sequences: acidic patch of ERKs (total of 16 amino-acids that interact directly with substrates). (ii) Domains on ERKs for binding to the DEF (FXFP) motifs of substrates [14], (total of 7 amino-acids that interact with substrates). B: Mouse and Anolis ERK sequences are highly similar. ERK1 protein sequences (top) and ERK2 protein sequences (bottom) from M. musculus and A. carolinensis are aligned side by side with the software multalin (http://multalin.toulouse.inra.fr/multalin/). Amino-acids in red are identical between mouse and anolis sequences, whereas amino-acids in black differ between mouse and anolis sequences. The percentage identity between sequences is calculated with the sequences after the arrow indicated in the figure (the N-terminal end of the molecules which is extremely variable in all vertebrates is not taken into account). C: 3D structures of human ERK1 and human ERK2 are highly similar, especially at the “face of the kinase”. Human ERK1 and human ERK2 were aligned by multalin program, and amino-acids that diverge between ERK1 and ERK2 are highlighted in yellow on 3D human ERK1 structure (PDB #4QTB). At ERK1 positions in the face of the kinase, the ERK2 equivalent amino-acids are indicated after the yellow arrows. Docking sites, activation phosphorylation sites and the dashed white line circling the “face of the kinase” are colored as presented for Fig. 5. i) front-side of the kinase where ATP-transfer occurs in the catalytic cleft between the two lobes ii) left-side of the kinase iii) back-side of the kinase iv) right-side of the kinase. D: 3D structure of anole lizard ERK2 is highly similar to rat ERK2. The amino-acid divergent between anole lizard ERK2 and human ERK2 are highlighted in yellow on 3D rat ERK2 structure (PDB #1ERK). Docking sites, activation phosphorylation sites and the dashed white line circling the “face of the kinase” are colored as presented for Fig. 5. E: Structures of anole lizard ERK1 is highly similar to human ERK1. The amino-acid divergent between anole lizard ERK1 and human ERK1 are highlighted in yellow on 3D human ERK1 structure (PDB #4QTB). Docking sites, activation phosphorylation sites and the dashed white line circling the “face of the kinase” are colored as presented for Fig. 5. The names of amino-acids of the “face of the kinase” that diverge are named in yellow, with the corresponding amino-acid of anole lizard named after the yellow arrows (differences occur only for conserved substitutions: serine/threonine and glutamic acid/aspactic acid). (PDF 2230 kb)