PDBsum entry 1f3h

Apoptosis

PDB id: 1f3h

Contents

Protein chain

136 a.a. *

Ligands

SO4 ×3

Metals

_ZN ×2

Waters ×90

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structure of the human anti-Apoptotic protein survivin reveals a dimeric arrangement.

Authors

M.A.Verdecia, H.Huang, E.Dutil, D.A.Kaiser, T.Hunter, J.P.Noel.

Ref.

Nat Struct Biol, 2000, 7, 602-608. [DOI no: 10.1038/76838]

PubMed id

10876248

Abstract

Survivin is a 16.5 kDa protein that is expressed during the G2/M phase of the cell cycle and is hypothesized to inhibit a default apoptotic cascade initiated in mitosis. This inhibitory function is coupled to survivin's localization to the mitotic spindle. To begin to address the structural basis of survivin's function, we report the X-ray crystal structure of a recombinant form of full length survivin to 2.58 A resolution. Survivin consists of two defined domains including an N-terminal Zn2+-binding BIR domain linked to a 65 A amphipathic C-terminal alpha-helix. The crystal structure reveals an extensive dimerization interface along a hydrophobic surface on the BIR domain of each survivin monomer. A basic patch acting as a sulfate/phosphate-binding module, an acidic cluster projecting off the BIR domain, and a solvent-accessible hydrophobic surface residing on the C-terminal amphipathic helix, are suggestive of functional protein-protein interaction surfaces.

Figure 2.
Figure 2. Overall architecture of human survivin. a, Ribbon representation of the survivin dimer. The Zn 2+ ion is shown as a shaded sphere. Coordination bonds are shown as dotted orange spheres. One monomer is blue; the other is rose. b, Orthogonal view of the ribbon representation shown in (a). c, Perspective and close up view of the Zn2+ binding site on one survivin monomer. The depicted orientation corresponds to that pictured in (a).

Figure 3.
Figure 3. Surface features of human survivin. a, GRASP36 representation of the survivin solvent accessible surface colored to approximately reflect the underlying electrostatic potential, where blue is positive, red is negative and white is neutral. Orientation is the same as in Fig. 2a. b, Orthogonal view of that shown in (a). c, Perspective and close up view of the sulfate binding site. The depicted orientation corresponds to that pictured in Fig. 2b. d, Expanded view of one survivin monomer illustrating the location of the 6 hydrophobic cluster.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 602-608) copyright 2000.