PDBsum entry 4yc7

Signaling protein

PDB id: 4yc7

Contents

Protein chains

291 a.a.

179 a.a.

Ligands

GNP

Metals

_MG

Waters ×63

PDB id:

4yc7

Name:

Signaling protein

Title:

Crystal structure of human fmnl2 gbd-fh3 domains bound to cdc42-gppnhp

Structure:

Formin-like protein 2. Chain: b. Fragment: unp residues 1-379. Synonym: formin homology 2 domain-containing protein 2, fmnl2. Engineered: yes. Cell division control protein 42 homolog. Chain: a. Fragment: unp residues 1-179. Synonym: g25k gtp-binding protein, cdc42.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fmnl2, fhod2, kiaa1902. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: cdc42. Expression_system_taxid: 562

Resolution:

2.50Å R-factor: 0.196 R-free: 0.253

Authors:

S.Kuhn,M.Geyer

Key ref:

S.Kühn et al. (2015). The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation. Nat Commun, 6, 7088. PubMed id: 25963737 DOI: 10.1038/ncomms8088

Date:

19-Feb-15 Release date: 13-May-15

Protein chain

Q96PY5  (FMNL2_HUMAN) -  Formin-like protein 2 from Homo sapiens

Seq: 1086 a.a.

Struc: 291 a.a.

Protein chain

P60953  (CDC42_HUMAN) -  Cell division control protein 42 homolog from Homo sapiens

Seq: 191 a.a.

Struc: 179 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 2: Chain A: E.C.3.6.5.2 - small monomeric GTPase.
• Reaction: GTP + H2O = GDP + phosphate + H⁺

GTP + H2O = GDP (Bound ligand (Het Group name = GNP) matches with 81.82% similarity) + phosphate + H(+)

• Enzyme class 3: Chain B: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/ncomms8088

Nat Commun 6:7088 (2015)

PubMed id: 25963737

The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation.

S.Kühn, C.Erdmann, F.Kage, J.Block, L.Schwenkmezger, A.Steffen, K.Rottner, M.Geyer.

ABSTRACT

Formins are actin polymerization factors that elongate unbranched actin filaments at the barbed end. Rho family GTPases activate Diaphanous-related formins through the relief of an autoregulatory interaction. The crystal structures of the N-terminal domains of human FMNL1 and FMNL2 in complex with active Cdc42 show that Cdc42 mediates contacts with all five armadillo repeats of the formin with specific interactions formed by the Rho-GTPase insert helix. Mutation of three residues within Rac1 results in a gain-of-function mutation for FMNL2 binding and reconstitution of the Cdc42 phenotype in vivo. Dimerization of FMNL1 through a parallel coiled coil segment leads to formation of an umbrella-shaped structure that-together with Cdc42-spans more than 15 nm in diameter. The two interacting FMNL-Cdc42 heterodimers expose six membrane interaction motifs on a convex protein surface, the assembly of which may facilitate actin filament elongation at the leading edge of lamellipodia and filopodia.