6X1R

Crystal Structure of Choanoflagellate (Monosiga brevicollis) Dlg1 PDZ2 (mbDLG-2) in spacegroup P212121

Summary for 6X1R

• Entry DOI: 10.2210/pdb6x1r/pdb
• Descriptor: mbDLG protein, GLYCEROL (3 entities in total)
• Functional Keywords: pdz, protein-protein interaction, choanoflagellates, monosiga brevicollis, peptide-binding domain, signaling protein
• Biological source: Monosiga brevicollis (Choanoflagellate)
• Total number of polymer chains: 1
• Total formula weight: 10939.32

Authors

Bamonte, H.A.,Amacher, J.F. (deposition date: 2020-05-19, release date: 2020-11-25, Last modification date: 2023-10-18)

Primary citation

Gao, M.,Mackley, I.G.P.,Mesbahi-Vasey, S.,Bamonte, H.A.,Struyvenberg, S.A.,Landolt, L.,Pederson, N.J.,Williams, L.I.,Bahl, C.D.,Brooks 3rd, L.,Amacher, J.F.
Structural characterization and computational analysis of PDZ domains in Monosiga brevicollis.
Protein Sci., 29:2226-2244, 2020

PubMed Abstract: Identification of the molecular networks that facilitated the evolution of multicellular animals from their unicellular ancestors is a fundamental problem in evolutionary cellular biology. Choanoflagellates are recognized as the closest extant nonmetazoan ancestors to animals. These unicellular eukaryotes can adopt a multicellular-like "rosette" state. Therefore, they are compelling models for the study of early multicellularity. Comparative studies revealed that a number of putative human orthologs are present in choanoflagellate genomes, suggesting that a subset of these genes were necessary for the emergence of multicellularity. However, previous work is largely based on sequence alignments alone, which does not confirm structural nor functional similarity. Here, we focus on the PDZ domain, a peptide-binding domain which plays critical roles in myriad cellular signaling networks and which underwent a gene family expansion in metazoan lineages. Using a customized sequence similarity search algorithm, we identified 178 PDZ domains in the Monosiga brevicollis proteome. This includes 11 previously unidentified sequences, which we analyzed using Rosetta and homology modeling. To assess conservation of protein structure, we solved high-resolution crystal structures of representative M. brevicollis PDZ domains that are homologous to human Dlg1 PDZ2, Dlg1 PDZ3, GIPC, and SHANK1 PDZ domains. To assess functional conservation, we calculated binding affinities for mbGIPC, mbSHANK1, mbSNX27, and mbDLG-3 PDZ domains from M. brevicollis. Overall, we find that peptide selectivity is generally conserved between these two disparate organisms, with one possible exception, mbDLG-3. Overall, our results provide novel insight into signaling pathways in a choanoflagellate model of primitive multicellularity.

PubMed: 32914530
DOI: 10.1002/pro.3947

Experimental method

X-RAY DIFFRACTION (1.3 Å)