PDBsum entry 4nen

Cell adhesion

PDB id: 4nen

Contents

Protein chains

1063 a.a.

665 a.a.

Ligands

NAG-NAG ×5

NAG-NAG-BMA-MAN-MAN-MAN

Metals

_CL

_MG ×2

_CA ×5

Waters ×128

PDB id:

4nen

Name:

Cell adhesion

Title:

An internal ligand-bound, metastable state of a leukocyte integrin, axb2

Structure:

Integrin alpha-x. Chain: a. Fragment: cd11c. Synonym: cd11 antigen-like family member c, leu m5, leukocyte adhesion glycoprotein p150,95 alpha chain, leukocyte adhesion receptor p150,95. Engineered: yes. Mutation: yes. Integrin beta-2.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: itgax, cd11c. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek-293. Gene: itgb2, cd18, mfi7.

Resolution:

2.90Å R-factor: 0.226 R-free: 0.264

Authors:

M.Sen,K.Yuki,T.A.Springer

Key ref:

M.Sen et al. (2013). An internal ligand-bound, metastable state of a leukocyte integrin, αXβ2. J Cell Biol, 203, 629-642. PubMed id: 24385486 DOI: 10.1083/jcb.201308083

Date:

29-Oct-13 Release date: 15-Jan-14

Protein chain

P20702  (ITAX_HUMAN) -  Integrin alpha-X from Homo sapiens

Seq: 1163 a.a.

Struc: 1063 a.a.*

Protein chain

P05107  (ITB2_HUMAN) -  Integrin beta-2 from Homo sapiens

Seq: 769 a.a.

Struc: 665 a.a.*

* PDB and UniProt seqs differ at 11 residue positions (black crosses)

DOI no: 10.1083/jcb.201308083

J Cell Biol 203:629-642 (2013)

PubMed id: 24385486

An internal ligand-bound, metastable state of a leukocyte integrin, αXβ2.

M.Sen, K.Yuki, T.A.Springer.

ABSTRACT

How is massive conformational change in integrins achieved on a rapid timescale? We report crystal structures of a metastable, putative transition state of integrin αXβ2. The αXβ2 ectodomain is bent; however, a lattice contact stabilizes its ligand-binding αI domain in a high affinity, open conformation. Much of the αI α7 helix unwinds, loses contact with the αI domain, and reshapes to form an internal ligand that binds to the interface between the β propeller and βI domains. Lift-off of the αI domain above this platform enables a range of extensional and rotational motions without precedent in allosteric machines. Movements of secondary structure elements in the β2 βI domain occur in an order different than in β3 integrins, showing that integrin β subunits can be specialized to assume different intermediate states between closed and open. Mutations demonstrate that the structure trapped here is metastable and can enable rapid equilibration between bent and extended-open integrin conformations and up-regulation of leukocyte adhesiveness.