PDBsum entry 1fho

Signaling protein

PDB id: 1fho

Contents

Protein chain

119 a.a.

PDB id:

1fho

Name:

Signaling protein

Title:

Solution structure of the ph domain from thE C. Elegans muscle protein unc-89

Structure:

Unc-89. Chain: a. Fragment: pleckstrin homology (ph) domain. Engineered: yes

Source:

Caenorhabditis elegans. Organism_taxid: 6239. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

25 models

Authors:

N.Blomberg,E.Baraldi,M.Sattler,M.Saraste,M.Nilges

Key ref:

N.Blomberg et al. (2000). Structure of a PH domain from the C. elegans muscle protein UNC-89 suggests a novel function. Structure, 8, 1079-1087. PubMed id: 11080629 DOI: 10.1016/S0969-2126(00)00509-8

Date:

02-Aug-00 Release date: 04-Oct-00

Protein chain

O01761  (UNC89_CAEEL) -  Muscle M-line assembly protein unc-89 from Caenorhabditis elegans

Seq: 8081 a.a.

Struc: 119 a.a.*

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

DOI no: 10.1016/S0969-2126(00)00509-8

Structure 8:1079-1087 (2000)

PubMed id: 11080629

Structure of a PH domain from the C. elegans muscle protein UNC-89 suggests a novel function.

N.Blomberg, E.Baraldi, M.Sattler, M.Saraste, M.Nilges.

ABSTRACT

BACKGROUND: Pleckstrin homology (PH) domains constitute a structurally conserved family present in many signaling and regulatory proteins. PH domains have been shown to bind to phospholipids, and many function in membrane targeting. They generally have a strong electrostatic polarization and interact with negatively charged phospholipids via the positive pole. On the basis of electrostatic modeling, however, we have previously identified a class of PH domains with a predominantly negative charge and predicted that these domains recognize other targets. Here, we report the first experimental structure of such a PH domain. RESULTS: The structure of the PH domain from Caenorhabditis elegans muscle protein UNC-89 has been determined by heteronuclear NMR. The domain adopts the classic PH fold, but has an unusual closed conformation of the "inositol binding loops. This creates a small opening to a deep hydrophobic pocket lined with negative charges on one side, and provides a molecular explanation for the lack of association with inositol-1,4,5-triphosphate. As predicted, the PH domain of UNC-89 has a strongly negative overall electrostatic potential. Modeling the Dbl homology (DH)-linked PH domains from the C. elegans genome shows that a large proportion of these modules are negatively charged. CONCLUSIONS: We present the first structure of a PH domain with a strong negative overall electrostatic potential. The presence of a deep pocket lined with negative charges suggests that the domain binds to ligands other than acidic phospholipids. The abundance of this class of PH domain in the C. elegans genome suggests a prominent role in mediating protein-protein interactions.

Selected figure(s)

Figure 5.
Figure 5. Charged Surface around Hydrophobic PocketCharged surface of the UNC-89 PH domain in the same orientation as in Figure 4 and (b) turned 90° so as to view the pocket between the b1-b2 and b3-b4 loop. Blue regions correspond to a positive surface potential, red to a negative. The arrow points into the opening of the hydrophobic pocket

The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 1079-1087) copyright 2000.

Figure was selected by an automated process.