4B6D

Structure of the atypical C1 domain of MgcRacGAP

4B6D の概要

• エントリーDOI: 10.2210/pdb4b6d/pdb
• 分子名称: RAC GTPASE-ACTIVATING PROTEIN 1, GLYCEROL, ZINC ION, ... (4 entities in total)
• 機能のキーワード: signaling protein, cytokinesis, plasma membrane, phospholipids, centralspindlin, spindle midzone, central spindle, midbody
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Nucleus: Q9H0H5
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 41816.59

構造登録者

Pye, V.E.,Lekomtsev, S.,Petronczki, M.,Cherepanov, P. (登録日: 2012-08-09, 公開日: 2012-12-12, 最終更新日: 2023-12-20)

主引用文献

Lekomtsev, S.,Su, K.,Pye, V.E.,Blight, K.,Sundaramoorthy, S.,Takaki, T.,Collinson, L.M.,Cherepanov, P.,Divecha, N.,Petronczki, M.
Centralspindlin Links the Mitotic Spindle to the Plasma Membrane During Cytokinesis.
Nature, 492:276-, 2012

PubMed Abstract: At the end of cell division, cytokinesis splits the cytoplasm of nascent daughter cells and partitions segregated sister genomes. To coordinate cell division with chromosome segregation, the mitotic spindle controls cytokinetic events at the cell envelope. The spindle midzone stimulates the actomyosin-driven contraction of the cleavage furrow, which proceeds until the formation of a microtubule-rich intercellular bridge with the midbody at its centre. The midbody directs the final membrane abscission reaction and has been proposed to attach the cleavage furrow to the intercellular bridge. How the mitotic spindle is connected to the plasma membrane during cytokinesis is not understood. Here we identify a plasma membrane tethering activity in the centralspindlin protein complex, a conserved component of the spindle midzone and midbody. We demonstrate that the C1 domain of the centralspindlin subunit MgcRacGAP associates with the plasma membrane by interacting with polyanionic phosphoinositide lipids. Using X-ray crystallography we determine the structure of this atypical C1 domain. Mutations in the hydrophobic cap and in basic residues of the C1 domain of MgcRacGAP prevent association of the protein with the plasma membrane, and abrogate cytokinesis in human and chicken cells. Artificial membrane tethering of centralspindlin restores cell division in the absence of the C1 domain of MgcRacGAP. Although C1 domain function is dispensable for the formation of the midzone and midbody, it promotes contractility and is required for the attachment of the plasma membrane to the midbody, a long-postulated function of this organelle. Our analysis suggests that centralspindlin links the mitotic spindle to the plasma membrane to secure the final cut during cytokinesis in animal cells.

PubMed: 23235882
DOI: 10.1038/NATURE11773

実験手法

X-RAY DIFFRACTION (2.2 Å)