PDBsum entry 3gmh

Cell cycle

PDB id: 3gmh

Contents

Protein chain

(+ 6 more) 193 a.a. *

Ligands

SO4 ×12

* Residue conservation analysis

PDB id:

3gmh

Name:

Cell cycle

Title:

Crystal structure of the mad2 dimer

Structure:

Mitotic spindle assembly checkpoint protein mad2a. Chain: a, b, c, d, e, f, g, h, i, j, k, l. Synonym: mad2-like 1, hsmad2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mad2, mad2a, mad2l1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.95Å R-factor: 0.220 R-free: 0.251

Authors:

E.Ozkan,X.Luo,M.Machius,H.Yu,J.Deisenhofer

Key ref:

M.Hara et al. (2015). Structure of an intermediate conformer of the spindle checkpoint protein Mad2. Proc Natl Acad Sci U S A, 112, 11252-11257. PubMed id: 26305957 DOI: 10.1073/pnas.1512197112

Date:

13-Mar-09 Release date: 17-Nov-10

Protein chains

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

Seq: 205 a.a.

Struc: 193 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1073/pnas.1512197112

Proc Natl Acad Sci U S A 112:11252-11257 (2015)

PubMed id: 26305957

Structure of an intermediate conformer of the spindle checkpoint protein Mad2.

M.Hara, E.Özkan, H.Sun, H.Yu, X.Luo.

ABSTRACT

The spindle checkpoint senses unattached kinetochores during prometaphase and inhibits the anaphase-promoting complex or cyclosome (APC/C), thus ensuring accurate chromosome segregation. The checkpoint protein mitotic arrest deficient 2 (Mad2) is an unusual protein with multiple folded states. Mad2 adopts the closed conformation (C-Mad2) in a Mad1-Mad2 core complex. In mitosis, kinetochore-bound Mad1-C-Mad2 recruits latent, open Mad2 (O-Mad2) from the cytosol and converts it to an intermediate conformer (I-Mad2), which can then bind and inhibit the APC/C activator cell division cycle 20 (Cdc20) as C-Mad2. Here, we report the crystal structure and NMR analysis of I-Mad2 bound to C-Mad2. Although I-Mad2 retains the O-Mad2 fold in crystal and in solution, its core structural elements undergo discernible rigid-body movements and more closely resemble C-Mad2. Residues exhibiting methyl chemical shift changes in I-Mad2 form a contiguous, interior network that connects its C-Mad2-binding site to the conformationally malleable C-terminal region. Mutations of residues at the I-Mad2-C-Mad2 interface hinder I-Mad2 formation and impede the structural transition of Mad2. Our study provides insight into the conformational activation of Mad2 and establishes the basis of allosteric communication between two distal sites in Mad2.