6X1X

PDZ domain from choanoflagellate GIPC (mbGIPC)

6X1X の概要

• エントリーDOI: 10.2210/pdb6x1x/pdb
• 分子名称: mbGIPC protein, GLYCEROL (3 entities in total)
• 機能のキーワード: pdz, protein-protein interaction, peptide-binding domain, choanoflagellate, monosiga brevicollis, signaling protein
• 由来する生物種: Monosiga brevicollis (Choanoflagellate)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10498.16

構造登録者

Gao, M.,Amacher, J.F. (登録日: 2020-05-19, 公開日: 2020-11-25, 最終更新日: 2023-10-18)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.198 Å)