PDBsum entry 2qyf

Cell cycle

PDB id: 2qyf

Contents

Protein chains

197 a.a. *

188 a.a. *

183 a.a. *

191 a.a. *

11 a.a. *

Ligands

SER-TRP-TYR-SER-TYR-PRO-PRO-PRO-GLN-ARG

Waters ×658

* Residue conservation analysis

PDB id:

2qyf

Name:

Cell cycle

Title:

Crystal structure of the mad2/p31(comet)/mad2-binding peptide ternary complex

Structure:

Mitotic spindle assembly checkpoint protein mad2a. Chain: a, c. Synonym: mad2-like 1, hsmad2. Engineered: yes. Mutation: yes. Mad2l1-binding protein. Chain: b, d. Fragment: unp residues 36-274. Synonym: caught by mad2 protein.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mad2l1, mad2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: mad2l1bp, cmt2, kiaa0110. Synthetic: yes. Other_details: synthetic 12-mer

Resolution:

2.30Å R-factor: 0.190 R-free: 0.257

Authors:

D.R.Tomchick,X.Luo

Key ref:

M.Yang et al. (2007). p31comet blocks Mad2 activation through structural mimicry. Cell, 131, 744-755. PubMed id: 18022368 DOI: 10.1016/j.cell.2007.08.048

Date:

14-Aug-07 Release date: 29-Jan-08

Protein chain

Q13257  (MD2L1_HUMAN) -  Mitotic spindle assembly checkpoint protein MAD2A from Homo sapiens

Seq: 205 a.a.

Struc: 197 a.a.*

Protein chain

Q15013  (MD2BP_HUMAN) -  MAD2L1-binding protein from Homo sapiens

Seq: 274 a.a.

Struc: 188 a.a.

Protein chain

Q13257  (MD2L1_HUMAN) -  Mitotic spindle assembly checkpoint protein MAD2A from Homo sapiens

Seq: 205 a.a.

Struc: 183 a.a.*

Protein chain

Q15013  (MD2BP_HUMAN) -  MAD2L1-binding protein from Homo sapiens

Seq: 274 a.a.

Struc: 191 a.a.

Protein chain

No UniProt id for this chain

Struc: 11 a.a.

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

DOI no: 10.1016/j.cell.2007.08.048

Cell 131:744-755 (2007)

PubMed id: 18022368

p31comet blocks Mad2 activation through structural mimicry.

M.Yang, B.Li, D.R.Tomchick, M.Machius, J.Rizo, H.Yu, X.Luo.

ABSTRACT

The status of spindle checkpoint signaling depends on the balance of two opposing dynamic processes that regulate the highly unusual two-state behavior of Mad2. In mitosis, a Mad1-Mad2 core complex recruits cytosolic Mad2 to kinetochores through Mad2 dimerization and converts Mad2 to a conformer amenable to Cdc20 binding, thereby facilitating checkpoint activation. p31(comet) inactivates the checkpoint through binding to Mad1- or Cdc20-bound Mad2, thereby preventing Mad2 activation and promoting the dissociation of the Mad2-Cdc20 complex. Here, we report the crystal structure of the Mad2-p31(comet) complex. The C-terminal region of Mad2 that undergoes rearrangement in different Mad2 conformers is a major structural determinant for p31(comet) binding, explaining the specificity of p31(comet) toward Mad1- or Cdc20-bound Mad2. p31(comet) adopts a fold strikingly similar to that of Mad2 and binds at the dimerization interface of Mad2. Thus, p31(comet) exploits the two-state behavior of Mad2 to block its activation by acting as an "anti-Mad2."

Selected figure(s)

Figure 4.
Figure 4. Interactions between Mad2 and p31^comet
(A) Ribbon diagrams of the Mad2-p31^comet complex. Two different views are shown to provide a clearer perspective of the Mad2-p31^comet interface. Helix αC in Mad2 is colored cyan to highlight its central role in establishing interactions between Mad2 and p31^comet. Three main patches of interactions at the Mad2-p31^comet interface are labeled and circled with red dashed lines.
(B–D) Interactions between Mad2 and p31^comet. The side chains of contacting residues are shown as sticks. Nitrogen and oxygen atoms are colored blue and red, respectively. Mad2 carbons are colored yellow and p31^comet carbons are colored gray and labeled in italics. The tightly bound water molecules are drawn as red spheres in (C).

Figure 6.
Figure 6. A Structural Model for the Blockage of Mad1-Assisted Mad2 Activation by p31^comet
(A) A structural model of the Mad1-Mad2-p31^comet complex. The Mad2 molecule in the Mad2-p31^comet complex was superimposed with the Mad2 molecules in the Mad1-Mad2 complex (PDB ID 1GO4). For clarity, the Mad2 monomers in the Mad1-Mad2 complex are omitted. Mad1 is colored green, with its Mad2-binding region colored red. The three interacting helices in Mad2-p31^comet are indicated.
(B) A surface representation to show that C-Mad2 uses a similar surface for the binding of p31^comet or O-Mad2. The p31^comet-binding residues of C-Mad2 are colored yellow, and the four key interacting residues, R133, Q134, R184 and F141, are colored red. The O-Mad2-binding residues of C-Mad2 are colored yellow. The same four residues R133, Q134, R184, and F141 (red) that are important for p31^comet binding are also involved in O-Mad2 binding.
(C) Ribbon diagram of the O-Mad2–C-Mad2 dimer (Mapelli et al., 2007). O-Mad2 is colored in cyan. C-Mad2 is colored blue with its C-terminal region shown in yellow. MBP1 is in red. The αC helices are labeled.
(D) Ribbon diagram of the Mad2-p31^comet complex with C-Mad2 in the same orientation as in (C).
(E) Overlay of ribbon diagrams of the O-Mad2–C-Mad2 dimer and the Mad2-p31^comet complex. The C-Mad2 molecules in both structures are superimposed. The color scheme is the same as in (C) and (D).

The above figures are reprinted from an Open Access publication published by Cell Press: Cell (2007, 131, 744-755) copyright 2007.

Figures were selected by the author.