PDBsum entry 4i1q

Cell adhesion

PDB id: 4i1q

Contents

Protein chain

200 a.a.

Waters ×62

PDB id:

4i1q

Name:

Cell adhesion

Title:

Crystal structure of hbrap1 n-bar domain

Structure:

Bridging integrator 2. Chain: a, b. Fragment: n-bar domain, unp residues 20-238. Synonym: breast cancer-associated protein 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: bin2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.53Å R-factor: 0.199 R-free: 0.252

Authors:

M.J.Sanchez-Barrena

Key ref:

M.J.Sánchez-Barrena et al. (2012). Bin2 is a membrane sculpting N-BAR protein that influences leucocyte podosomes, motility and phagocytosis. Plos One, 7, e52401. PubMed id: 23285027

Date:

21-Nov-12 Release date: 06-Feb-13

Protein chains

Q9UBW5  (BIN2_HUMAN) -  Bridging integrator 2 from Homo sapiens

Seq: 565 a.a.

Struc: 200 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.?

Plos One 7:e52401 (2012)

PubMed id: 23285027

Bin2 is a membrane sculpting N-BAR protein that influences leucocyte podosomes, motility and phagocytosis.

M.J.Sánchez-Barrena, Y.Vallis, M.R.Clatworthy, G.J.Doherty, D.B.Veprintsev, P.R.Evans, H.T.McMahon.

ABSTRACT

Cell motility, adhesion and phagocytosis are controlled by actin and membrane remodelling processes. Bridging integrator-2 (Bin2) also called Breast cancer-associated protein 1 (BRAP1) is a predicted N-BAR domain containing protein with unknown function that is highly expressed in leucocytic cells. In the present study we solved the structure of Bin2 BAR domain and studied its membrane binding and bending properties in vitro and in vivo. Live-cell imaging experiments showed that Bin2 is associated with actin rich structures on the plasma membrane, where it was targeted through its N-BAR domain. Pull-down experiments and immunoprecipitations showed that Bin2 C-terminus bound SH3 domain containing proteins such as Endophilin A2 and α-PIX. siRNA of endogenous protein led to decreased cell migration, increased phagocytosis and reduced podosome density and dynamics. In contrast, overexpression of Bin2 led to decreased phagocytosis and increased podosome density and dynamics. We conclude that Bin2 is a membrane-sculpting protein that influences podosome formation, motility and phagocytosis in leucocytes. Further understanding of this protein may be key to understand the behaviour of leucocytes under physiological and pathological conditions.