PDBsum entry 2m8s

Chaperone/membrane protein

PDB id: 2m8s

Contents

Protein chains

97 a.a.

24 a.a.

PDB id:

2m8s

Name:

Chaperone/membrane protein

Title:

Nmr structure of the cytoplasmic tail of the membrane form of heparin- binding egf-like growth factor (prohb-egf-ct) complexed with the ubiquitin homology domain of bcl-2-associated athanogene 1 from mus musculus (mbag-1-ubh)

Structure:

Bag family molecular chaperone regulator 1. Chain: a. Fragment: unp residues 137-233. Synonym: bag-1, bcl-2-associated athanogene 1. Engineered: yes. Proheparin-binding egf-like growth factor. Chain: b. Fragment: unp residues 185-208. Synonym: heparin-binding egf-like growth factor, hb-egf, hbegf,

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: bag1. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.

NMR struc:

18 models

Authors:

H.W.Huang,C.Yu

Key ref:

K.W.Hung et al. (2014). Nuclear magnetic resonance structure of the cytoplasmic tail of heparin binding EGF-like growth factor (proHB-EGF-CT) complexed with the ubiquitin homology domain of Bcl-2-associated athanogene 1 from Mus musculus (mBAG-1-UBH). Biochemistry, 53, 1935-1946. PubMed id: 24628338 DOI: 10.1021/bi5003019

Date:

03-Jun-13 Release date: 16-Apr-14

Protein chain

Q60739  (BAG1_MOUSE) -  BAG family molecular chaperone regulator 1 from Mus musculus

Seq: 355 a.a.

Struc: 97 a.a.

Protein chain

Q99075  (HBEGF_HUMAN) -  Proheparin-binding EGF-like growth factor from Homo sapiens

Seq: 208 a.a.

Struc: 24 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1021/bi5003019

Biochemistry 53:1935-1946 (2014)

PubMed id: 24628338

Nuclear magnetic resonance structure of the cytoplasmic tail of heparin binding EGF-like growth factor (proHB-EGF-CT) complexed with the ubiquitin homology domain of Bcl-2-associated athanogene 1 from Mus musculus (mBAG-1-UBH).

K.W.Hung, H.W.Huang, C.C.Cho, S.C.Chang, C.Yu.

ABSTRACT

The membrane form of heparin binding EGF-like growth factor (proHB-EGF) yields secreted HB-EGF and a membrane-anchored cytoplasmic tail (proHB-EGF-CT), which may be targeted to the nuclear membrane after a shedding stimulus. Bcl-2-associated athanogene 1 (BAG-1) accumulates in the nuclei and inhibits apoptosis in adenoma-derived cell lines. The maintenance of high levels of nuclear BAG-1 enhances cell survival. However, the ubiquitin homology domain of BAG-1 from Mus musculus (mBAG-1-UBH) is proposed to interact with proHB-EGF-CT, and this interaction may enhance the cytoprotection against the apoptosis inducer. The mechanism of the synergistic anti-apoptosis function of proHB-EGF-CT and mBAG-1-UBH is still unknown. We offer a hypothesis that proHB-EGF-CT can maintain high levels of nuclear BAG-1. In this study, we first report the three-dimensional nuclear magnetic resonance structure of proHB-EGF-CT complexed with mBAG-1-UBH. In the structure of the complex, the residues in the C-terminus and one turn between β-strands β1 and β2 of mBAG-1-UBH bind to two terminals of proHB-EGF-CT, which folds into a loop with end-to-end contact. This end-to-end folding of proHB-EGF-CT causes the basic amino acids to colocalize and form a positively charged groove. The dominant forces in the binding interface between proHB-EGF-CT and mBAG-1-UBH are charge-charge interactions. On the basis of our mutagenesis results, the basic amino acid cluster in the N-terminus of proHB-EGF-CT is the crucial binding site for mBAG-1-UBH, whereas another basic amino acid in the C-terminus facilitates this interaction. Interestingly, the mBAG-1-UBH binding region on the proHB-EGF-CT peptide is also involved in the region found to be important for nuclear envelope targeting, supporting the hypothesis that proHB-EGF-CT is most likely able to trigger the nuclear translocation of BAG-1 in keeping its level high.