PDBsum entry 4lmm

Protein binding

PDB id: 4lmm

Contents

Protein chain

91 a.a.

Ligands

ACY

Metals

_CL

Waters ×129

PDB id:

4lmm

Name:

Protein binding

Title:

Crystal structure of nherf1 pdz1 domain complexed with the cxcr2 c- terminal tail in p21 space group

Structure:

Na(+)/h(+) exchange regulatory cofactor nhe-rf1. Chain: a. Fragment: unp residues 11-95. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nherf, nherf1, slc9a3r1. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.10Å R-factor: 0.190 R-free: 0.217

Authors:

Y.Jiang,G.Lu,Y.Wu,J.Brunzelle,N.Sirinupong,C.Li,Z.Yang

Key ref:

Y.Jiang et al. (2013). New conformational state of NHERF1-CXCR2 signaling complex captured by crystal lattice trapping. Plos One, 8, e81904. PubMed id: 24339979 DOI: 10.1371/journal.pone.0081904

Date:

10-Jul-13 Release date: 15-Jan-14

Protein chain

O14745  (NHRF1_HUMAN) -  Na(+)/H(+) exchange regulatory cofactor NHE-RF1 from Homo sapiens

Seq: 358 a.a.

Struc: 91 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1371/journal.pone.0081904

Plos One 8:e81904 (2013)

PubMed id: 24339979

New conformational state of NHERF1-CXCR2 signaling complex captured by crystal lattice trapping.

Y.Jiang, G.Lu, L.R.Trescott, Y.Hou, X.Guan, S.Wang, A.Stamenkovich, J.Brunzelle, N.Sirinupong, C.Li, Z.Yang.

ABSTRACT

NHERF1 is a PDZ adaptor protein that scaffolds the assembly of diverse signaling complexes and has been implicated in many cancers. However, little is known about the mechanism responsible for its scaffolding promiscuity or its ability to bind to multiple targets. Computational studies have indicated that PDZ promiscuity may be attributed to its conformational dynamics, but experimental evidence for this relationship remains very limited. Here we examine the conformational flexibility of the NHERF1 PDZ1 domain using crystal lattice trapping via solving PDZ1 structure of a new crystal form. The structure, together with prior PDZ1 structures of a different space group, reveals that 4 of 11 ligand-interacting residues undergo significant crystal packing-induced structural changes. Most of these residues correspond to the residues involved in allosteric transition when a peptide ligand binds. In addition, a subtle difference in ligand conformations causes the same peptide to bind in slightly different modes in different crystal forms. These findings indicate that substantial structural flexibility is present in the PDZ1 peptide-binding pocket, and the structural substate trapped in the present crystal form can be utilized to represent the conformational space accessible to the protein. Such knowledge will be critical for drug design against the NHERF1 PDZ1 domain, highlighting the continued need for experimentally determined PDZ1-ligand complexes.