6QNN

CLATHRIN HEAVY CHAIN N-TERMINAL DOMAIN BOUND TO GTSE1 LIDL MOTIF

Summary for 6QNN

• Entry DOI: 10.2210/pdb6qnn/pdb
• Descriptor: Clathrin heavy chain 1, G2 and S phase-expressed protein 1 (3 entities in total)
• Functional Keywords: beta-propeller, clathrin-box, lidl-motif, cell cycle
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 47626.59

Authors

Porfetye, A.T.,Lin, Y.,Vetter, I.R. (deposition date: 2019-02-11, release date: 2019-08-28, Last modification date: 2024-01-24)

Primary citation

Rondelet, A.,Lin, Y.C.,Singh, D.,Porfetye, A.T.,Thakur, H.C.,Hecker, A.,Brinkert, P.,Schmidt, N.,Bendre, S.,Muller, F.,Mazul, L.,Widlund, P.O.,Bange, T.,Hiller, M.,Vetter, I.R.,Bird, A.W.
Clathrin's adaptor interaction sites are repurposed to stabilize microtubules during mitosis.
J.Cell Biol., 219:-, 2020

PubMed Abstract: Clathrin ensures mitotic spindle stability and efficient chromosome alignment, independently of its vesicle trafficking function. Although clathrin localizes to the mitotic spindle and kinetochore fiber microtubule bundles, the mechanisms by which clathrin stabilizes microtubules are unclear. We show that clathrin adaptor interaction sites on clathrin heavy chain (CHC) are repurposed during mitosis to directly recruit the microtubule-stabilizing protein GTSE1 to the spindle. Structural analyses reveal that these sites interact directly with clathrin-box motifs on GTSE1. Disruption of this interaction releases GTSE1 from spindles, causing defects in chromosome alignment. Surprisingly, this disruption destabilizes astral microtubules, but not kinetochore-microtubule attachments, and chromosome alignment defects are due to a failure of chromosome congression independent of kinetochore-microtubule attachment stability. GTSE1 recruited to the spindle by clathrin stabilizes microtubules by inhibiting the microtubule depolymerase MCAK. This work uncovers a novel role of clathrin adaptor-type interactions to stabilize nonkinetochore fiber microtubules to support chromosome congression, defining for the first time a repurposing of this endocytic interaction mechanism during mitosis.

PubMed: 31932847
DOI: 10.1083/jcb.201907083

Experimental method

X-RAY DIFFRACTION (2.03 Å)