Summer Research Fellowship Programme of India's Science Academies 2017
Purification and characterisation of survivin homologs
Sanjogta Koul
School of Biotechnology, University of Jammu
Guided by
Dr. Shekhar C. Mande
Lab of Structural Biology, National Centre for Cell Sciences, Pune 411007
1. Introduction
Human survivin is a 16.5 kDa i.e., 142 amino acid protein. It is a member of inhibitor of apoptosis
protein (IAP) family. It is mainly expressed during the G
M phase of the cell cycle and is hypothesized
to inhibit many apoptotic cascades. It is generally overexpressed in tumour cells.
1.1. Structure of survivin
The structure of human survivin consists of N-terminal Zn
- binding BIR (Baculovirus IAP Repeat)
domain which is linked to a 65 Å amphipathic C-terminal alpha-helix.
In the BIR domain, three stranded antiparallel β-sheets are present which are surrounded by four small
α-helices. In this BIR domain a Zn
ion is present which is tetrahedrally coordinated by Cys 57, Cys
60, His 77, and Cys 84 bridges the core β-sheet with α4 and α5 helices [1].
Survivin’s unique feature is the presence of a 65 Å long C-terminal helix, α6, residues 100–140. Both
hydrogen bonding and hydrophobic interactions stabilize and fixes the direction of helical cord
between the BIR domain and residues of α6.
Human survivin exists as a dimer when alone and forms a bow-tie shaped dimer between the two α6
helices and form an 110° angle approximately with a tip-to-tip interhelical distance of 111 Å. But when
it is alone [2].
Fig. 1. Overall architecture of human survivin. (a) Ribbon representation of the survivin dimer. The
Zn2+ 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) [1].
1.2. Interaction of Survivin with other proteins
Survivin when exists as a monomer, interacts by hydrophobic interactionswith INCENP, Borealin and
aurora kinase B (AUKB) and forms chromosomal passenger complex (CPC) thus participating in cell