PDBsum entry 5a6c

Cell adhesion

PDB id: 5a6c

Contents

Protein chains

363 a.a.

Ligands

SO4 ×3

PDB id:

5a6c

Name:

Cell adhesion

Title:

Concomitant binding of afadin to lgn and f-actin directs planar spindle orientation

Structure:

G-protein-signaling modulator 2, afadin. Chain: a, b. Fragment: lgn tpr domain residues 15-350, afadin residues 1719-1756. Engineered: yes. Other_details: fusion protein spanning residues 15-350 of human lgn and residues 1709-1746 of afadin

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: gpsm2, lgn, mllt4, af6. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta.

Resolution:

2.90Å R-factor: 0.208 R-free: 0.252

Authors:

M.Carminati,S.Gallini,L.Pirovano,A.Alfieri,S.Bisi,M.Mapelli

Key ref:

M.Carminati et al. (2016). Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation. Nat Struct Biol, 23, 155-163. PubMed id: 26751642 DOI: 10.1038/nsmb.3152

Date:

25-Jun-15 Release date: 30-Dec-15

Protein chains

P55196  (AFAD_HUMAN) -  Afadin from Homo sapiens

Seq: 1824 a.a.

Struc: 363 a.a.*

Protein chains

P81274  (GPSM2_HUMAN) -  G-protein-signaling modulator 2 from Homo sapiens

Seq: 684 a.a.

Struc: 363 a.a.*

* PDB and UniProt seqs differ at 343 residue positions (black crosses)

DOI no: 10.1038/nsmb.3152

Nat Struct Biol 23:155-163 (2016)

PubMed id: 26751642

Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation.

M.Carminati, S.Gallini, L.Pirovano, A.Alfieri, S.Bisi, M.Mapelli.

ABSTRACT

Polarized epithelia form by oriented cell divisions in which the mitotic spindle aligns parallel to the epithelial plane. To orient the mitotic spindle, cortical cues trigger the recruitment of NuMA-dynein-based motors, which pull on astral microtubules via the protein LGN. We demonstrate that the junctional protein Afadin is required for spindle orientation and correct epithelial morphogenesis of Caco-2 cysts. Molecularly, Afadin binds directly and concomitantly to F-actin and to LGN. We determined the crystallographic structure of human Afadin in complex with LGN and show that it resembles the LGN-NuMA complex. In mitosis, Afadin is necessary for cortical accumulation of LGN and NuMA above the spindle poles, in an F-actin-dependent manner. Collectively, our results depict Afadin as a molecular hub governing the enrichment of LGN and NuMA at the cortex. To our knowledge, Afadin is the first-described mechanical anchor between dynein and cortical F-actin.