PDBsum entry 4ddp

Membrane protein

PDB id

4ddp

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Contents

			Protein chain

					195 a.a.

			Waters ×115

PDB id:

4ddp

Links

Name:

Membrane protein

Title:

Crystal structure of beclin 1 evolutionarily conserved domain(ecd)

Structure:

Beclin-1. Chain: a. Fragment: unp residues 241-450. Synonym: coiled-coil myosin-like bcl2-interacting protein, protein gt197. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: becn1, gt197. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.55Å

R-factor:

0.177

R-free:

0.203

Authors:

W.J.Huang,W.Y.Choi,J.W.Wang,Y.G.Shi

Key ref:

W.Huang et al. (2012). Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein. Cell Res, 22, 473-489. PubMed id: 22310240

Date:

19-Jan-12

Release date:

22-Feb-12

PROCHECK

	Headers

	References

Protein chain

Q14457 (BECN1_HUMAN) - Beclin-1 from Homo sapiens

Seq: Struc:					450 a.a. 195 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.?

[IntEnz] [ExPASy] [KEGG] [BRENDA]

	Cell Res 22:473-489 (2012)
PubMed id: 22310240

Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein.
W.Huang, W.Choi, W.Hu, N.Mi, Q.Guo, M.Ma, M.Liu, Y.Tian, P.Lu, F.L.Wang, H.Deng, L.Liu, N.Gao, L.Yu, Y.Shi.

ABSTRACT

The Beclin 1 gene is a haplo-insufficient tumor suppressor and plays an essential role in autophagy. However, the molecular mechanism by which Beclin 1 functions remains largely unknown. Here we report the crystal structure of the evolutionarily conserved domain (ECD) of Beclin 1 at 1.6 Å resolution. Beclin 1 ECD exhibits a previously unreported fold, with three structural repeats arranged symmetrically around a central axis. Beclin 1 ECD defines a novel class of membrane-binding domain, with a strong preference for lipid membrane enriched with cardiolipin. The tip of a surface loop in Beclin 1 ECD, comprising three aromatic amino acids, acts as a hydrophobic finger to associate with lipid membrane, consequently resulting in the deformation of membrane and liposomes. Mutation of these aromatic residues rendered Beclin 1 unable to stably associate with lipid membrane in vitro and unable to fully rescue autophagy in Beclin 1-knockdown cells in vivo. These observations form an important framework for deciphering the biological functions of Beclin 1.

Literature references that cite this PDB file's key reference

PubMed id

Reference

23364696

S.Shoji-Kawata, R.Sumpter, M.Leveno, G.R.Campbell, Z.Zou, L.Kinch, A.D.Wilkins, Q.Sun, K.Pallauf, D.MacDuff, C.Huerta, H.W.Virgin, J.B.Helms, R.Eerland, S.A.Tooze, R.Xavier, D.J.Lenschow, A.Yamamoto, D.King, O.Lichtarge, N.V.Grishin, S.A.Spector, D.V.Kaloyanova, and B.Levine (2013).
Identification of a candidate therapeutic autophagy-inducing peptide.

Nature, 494, 201-206.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.