PDBsum entry 1k3k

Apoptosis

PDB id: 1k3k

Contents

Protein chain

146 a.a. *

* Residue conservation analysis

PDB id:

1k3k

Name:

Apoptosis

Title:

Solution structure of a bcl-2 homolog from kaposi's sarcoma virus

Structure:

Functional anti-apoptotic factor vbcl-2 homolog. Chain: a. Engineered: yes. Mutation: yes

Source:

Human herpesvirus 8. Organism_taxid: 37296. Expressed in: escherichia coli. Expression_system_taxid: 562

NMR struc:

1 models

Authors:

Q.Huang,A.M.Petros,H.W.Virgin,S.W.Fesik,E.T.Olejniczak

Key ref:

Q.Huang et al. (2002). Solution structure of a Bcl-2 homolog from Kaposi sarcoma virus. Proc Natl Acad Sci U S A, 99, 3428-3433. PubMed id: 11904405 DOI: 10.1073/pnas.062525799

Date:

03-Oct-01 Release date: 10-Apr-02

Protein chain

Q76RI8  (Q76RI8_HHV8) -  Bcl-2 from Human herpesvirus 8

Seq: 175 a.a.

Struc: 146 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1073/pnas.062525799

Proc Natl Acad Sci U S A 99:3428-3433 (2002)

PubMed id: 11904405

Solution structure of a Bcl-2 homolog from Kaposi sarcoma virus.

Q.Huang, A.M.Petros, H.W.Virgin, S.W.Fesik, E.T.Olejniczak.

ABSTRACT

Kaposi sarcoma-associated herpes virus (KSHV) contains a gene that has functional and sequence homology to the apoptotic Bcl-2 family of proteins [Sarid, R., Sato, T., Bohenzky, R. A., Russo, J. J. & Chang, Y. (1997) Nat. Med. 3, 293-298]. The viral Bcl-2 protein promotes survival of infected cells and may contribute to the development of Kaposi sarcoma tumors [Boshoff, C. & Chang, Y. (2001) Annu. Rev. Med. 52, 453-470]. Here we describe the solution structure of the viral Bcl-2 homolog from KSHV. Comparison of the KSHV Bcl-2 structure to that of Bcl-2 and Bcl-x(L) shows that although the overall fold is the same, there are key differences in the lengths of the helices and loops. Binding studies on peptides derived from the Bcl-2 homology region 3 of proapoptotic family members indicate that the specificity of the viral protein is very different from what was previously observed for Bcl-x(L) and Bcl-2, suggesting that the viral protein has evolved to have a different mechanism of action than the host proteins.

Selected figure(s)

Figure 2.
Fig. 2. (A) Backbone (N,C^ ,C') superposition of 10 low-energy NMR-derived structures for viral KSHV Bcl-2. Helices are numbered with respect to those observed in the structure of Bcl-x[L]. (B) Ribbon (36) depiction of the average-minimized structure for viral KSHV Bcl-2. The central helix, 5, is colored yellow. (C) Solvent-accessible surface showing hydrophobic groove for viral KSHV Bcl-2. Leucine, isoleucine, valine, methionine, tyrosine, phenylalanine, and tryptophan residues are colored yellow. Aspartate and glutamate are colored red. Lysine, arginine, and histidine are colored blue. All other residue types are colored gray.

Figure 3.
Fig. 3. Comparison of KSHV Bcl-2 (A) to Bcl-x[L] (B) and to Bcl-2 (C). Residues of the hydrophobic groove that are homologous to those that contact the Bak and Bad peptides when complexed to Bcl-x[L] are shown along with the tryptophan residue of the NWGR sequence. To emphasize the differences in the structured regions of the proteins, we have made our comparisons to truncated forms of Bcl-2 and Bcl-x[L] (17, 18).

Figures were selected by the author.