PDBsum entry 4dx9

Protein binding

PDB id: 4dx9

Contents

Protein chains

106 a.a.

110 a.a.

105 a.a.

127 a.a.

(+ 9 more) 11 a.a.

118 a.a.

127 a.a.

91 a.a.

113 a.a.

104 a.a.

(+ 1 more) 127 a.a.

63 a.a.

47 a.a.

129 a.a.

116 a.a.

102 a.a.

99 a.a.

102 a.a.

106 a.a.

120 a.a.

101 a.a.

101 a.a.

128 a.a.

49 a.a.

12 a.a.

93 a.a.

Ligands

SER-ALA-VAL

VAL-ASN-PRO-LYS ×2

SER-ALA-VAL-THR

LYS-SER-ALA-VAL-THR-THR-VAL-VAL

VAL-VAL-ASN-PRO-LYS

LYS-SER-ALA-VAL-THR-THR-VAL-VAL-ASN-PRO ×4

SER-ALA-VAL-THR-THR-VAL-VAL-ASN

ASN-PRO

LYS-SER-ALA-VAL ×2

ALA-VAL-THR-THR-VAL-VAL-ASN-PRO

THR-VAL-VAL-ASN-PRO

PDB id:

4dx9

Name:

Protein binding

Title:

Icap1 in complex with integrin beta 1 cytoplasmic tail

Structure:

Integrin beta-1-binding protein 1. Chain: a, 0, k, m, 1, c, 2, e, 3, g, o, q, i, 4, k, 5, m, o, a, s, u, c, e, g, i, q, s, u, w, w, y, y. Fragment: ptb domain. Synonym: integrin cytoplasmic domain-associated protein 1, icap-1. Engineered: yes. Integrin beta-1. Chain: l, n, x, d, 8, h, p, b, 9, f, r, j, 7, l, 6, n, p, t, v, b, d, f, h, j, r, t, v, x, z, z.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: icap1, integrin cytoplasmic domain-associated protein 1 (icap1), itgb1bp1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.99Å R-factor: 0.255 R-free: 0.312

Authors:

W.Liu,K.Draheim,R.Zhang,D.A.Calderwood,T.J.Boggon

Key ref:

W.Liu et al. (2013). Mechanism for KRIT1 release of ICAP1-mediated suppression of integrin activation. Mol Cell, 49, 719-729. PubMed id: 23317506 DOI: 10.1016/j.molcel.2012.12.005

Date:

27-Feb-12 Release date: 09-Jan-13

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 106 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 110 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 105 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 127 a.a.

Protein chains

P05556  (ITB1_HUMAN) -  Integrin beta-1 from Homo sapiens

Seq: 798 a.a.

Struc: 11 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 118 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 127 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 91 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 113 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 104 a.a.

Protein chains

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 127 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 63 a.a.*

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 47 a.a.*

Protein chains

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 129 a.a.*

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 116 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 102 a.a.*

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 99 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 102 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 106 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 120 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 101 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 101 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 128 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 49 a.a.*

Protein chain

P05556  (ITB1_HUMAN) -  Integrin beta-1 from Homo sapiens

Seq: 798 a.a.

Struc: 12 a.a.

Protein chain

O14713  (ITBP1_HUMAN) -  Integrin beta-1-binding protein 1 from Homo sapiens

Seq: 200 a.a.

Struc: 93 a.a.

* PDB and UniProt seqs differ at 21 residue positions (black crosses)

DOI no: 10.1016/j.molcel.2012.12.005

Mol Cell 49:719-729 (2013)

PubMed id: 23317506

Mechanism for KRIT1 release of ICAP1-mediated suppression of integrin activation.

W.Liu, K.M.Draheim, R.Zhang, D.A.Calderwood, T.J.Boggon.

ABSTRACT

KRIT1 (Krev/Rap1 Interaction Trapped-1) mutations are observed in ∼40% of autosomal-dominant cerebral cavernous malformations (CCMs), a disease occurring in up to 0.5% of the population. We show that KRIT1 functions as a switch for β1 integrin activation by antagonizing ICAP1 (Integrin Cytoplasmic Associated Protein-1)-mediated modulation of "inside-out" activation. We present cocrystal structures of KRIT1 with ICAP1 and ICAP1 with integrin β1 cytoplasmic tail to 2.54 and 3.0 Å resolution (the resolutions at which I/σI = 2 are 2.75 and 3.0 Å, respectively). We find that KRIT1 binds ICAP1 by a bidentate surface, that KRIT1 directly competes with integrin β1 to bind ICAP1, and that KRIT1 antagonizes ICAP1-modulated integrin activation using this site. We also find that KRIT1 contains an N-terminal Nudix domain, in a region previously designated as unstructured. We therefore provide insights to integrin regulation and CCM-associated KRIT1 function.