PDBsum entry 2d4c

Transferase

PDB id: 2d4c

Contents

Protein chains

224 a.a. *

Metals

_CA

Waters ×197

* Residue conservation analysis

PDB id:

2d4c

Name:

Transferase

Title:

Crystal structure of the endophilin bar domain mutant

Structure:

Sh3-containing grb2-like protein 2. Chain: a, b, c, d. Fragment: endophilin a1 bar domain. Synonym: sh3 domain protein 2a, endophilin 1, een-b1. Engineered: yes

Source:

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

Biol. unit:

Dimer (from PQS)

Resolution:

2.40Å R-factor: 0.215 R-free: 0.270

Authors:

M.Masuda,S.Takeda

Key ref:

M.Masuda et al. (2006). Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms. EMBO J, 25, 2889-2897. PubMed id: 16763557 DOI: 10.1038/sj.emboj.7601176

Date:

13-Oct-05 Release date: 11-Jul-06

Protein chains

Q99962  (SH3G2_HUMAN) -  Endophilin-A1 from Homo sapiens

Seq: 352 a.a.

Struc: 224 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.3.1.- - ?????

DOI no: 10.1038/sj.emboj.7601176

EMBO J 25:2889-2897 (2006)

PubMed id: 16763557

Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms.

M.Masuda, S.Takeda, M.Sone, T.Ohki, H.Mori, Y.Kamioka, N.Mochizuki.

ABSTRACT

The crescent-shaped BAR (Bin/Amphiphysin/Rvs-homology) domain dimer is a versatile protein module that senses and generates positive membrane curvature. The BAR domain dimer of human endophilin-A1, solved at 3.1 A, has a unique structure consisting of a pair of helix-loop appendages sprouting out from the crescent. The appendage's short helices form a hydrophobic ridge, which runs across the concave surface at its center. Examining liposome binding and tubulation in vitro using purified BAR domain and its mutants indicated that the ridge penetrates into the membrane bilayer and enhances liposome tubulation. BAR domain-expressing cells exhibited marked plasma membrane tubulation in vivo. Furthermore, a swinging-arm mutant lost liposome tubulation activity yet retaining liposome binding. These data suggested that the rigid crescent dimer shape is crucial for the tubulation. We here propose that the BAR domain drives membrane curvature by coordinate action of the crescent's scaffold mechanism and the ridge's membrane insertion in addition to membrane binding via amino-terminal amphipathic helix.

Selected figure(s)

Figure 6.
Figure 6 Close-up of helix 0 in an a4 mutant monomer (orange). The same superimposition as in Figure 5C but viewed from the side and displays the helix 0. The helix 0 is disordered in the wild-type structure (blue). The side chains of N-terminal residues are shown (H11KATQKVSEKVGGAEGTKL29 in the a4 and G26TKL in the wild type). The amphipathic helix 0 is stabilized by hydrophobic interactions with the helix II and III and also by hydrogen bonds with a symmetrical molecule.

Figure 8.
Figure 8 Two potential mechanisms for driving membrane curvature by endophilin-A1. (A) Kissing adhesion of an N-BAR domain on planar lipid bilayer. The helix 0 is essential for the membrane binding. Membrane insertion of the helix 0 is supposed. (B) Insertion of hydrophobic portions of macromolocules into one leaflet can create bilayer surface discrepancy that causes membrane curvature. (C) The simple N-BAR domain, such as amphiphysin and App, induces membrane curvature by impressing the concave surface onto the membrane. The rigidity of the molecule is required for this mechanism. (D) To drive membrane curvature, the endophilin N-BAR domain uses both the rigid crescent shape-mediated deformation and the insertion of hydrophobic ridge on the concave surface in addition to kissing adhesion of N-BAR to membrane surface.

The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2006, 25, 2889-2897) copyright 2006.

Figures were selected by an automated process.