PDBsum entry 1vig

Ribonucleoprotein

PDB id: 1vig

Contents

Protein chain

71 a.a.

References listed in PDB file

Key reference

Title

Three-Dimensional structure and stability of the kh domain: molecular insights into the fragile X syndrome.

Authors

G.Musco, G.Stier, C.Joseph, M.A.Castiglione morelli, M.Nilges, T.J.Gibson, A.Pastore.

Ref.

Cell, 1996, 85, 237-245. [DOI no: 10.1016/S0092-8674(00)81100-9]

PubMed id

8612276

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a percentage match of 96%.

Abstract

The KH module is a sequence motif found in a number of proteins that are known to be in close association with RNA. Experimental evidence suggests a direct involvement of KH in RNA binding. The human FMR1 protein, which has two KH domains, is associated with fragile X syndrome, the most common inherited cause of mental retardation. Here we present the three-dimensional solution structure of the KH module. The domain consists of a stable beta alpha alpha beta beta alpha fold. On the basis of our results, we suggest a potential surface for RNA binding centered on the loop between the first two helices. Substitution of a well-conserved hydrophobic residue located on the second helix destroys the KH fold; a mutation of this position in FMR1 leads to an aggravated fragile X phenotype.

Figure 4.
Figure 4. Suggested Surface for RNA RecognitionMOLSCRIPT representation of the Vig-6 domain, showing conserved positive charges (light blue) and the backbone of the GkxG loop (yellow).

Figure 5.
Figure 5. Models of the Two KH Repeats of FMR1Models are based on the coordinates of the Vig-6 average structure and the new sequence alignment (Figure 3). Coloring is as follows: magenta, the backbone atoms; green, the hydrophobic side chains; yellow, the position affected by the mutation (isoleucine to asparagine) at residues Ile-241 and Ile-304) of the FMR1 protein.

The above figures are reprinted by permission from Cell Press: Cell (1996, 85, 237-245) copyright 1996.

Secondary reference #1

Title

The kh module has an alpha beta fold.

Authors

M.A.Castiglone morelli, G.Stier, T.Gibson, C.Joseph, G.Musco, A.Pastore, G.Travè.

Ref.

Febs Lett, 1995, 358, 193-198. [DOI no: 10.1016/0014-5793(94)01422-W]

PubMed id

7828735

Figure 1.
Fig. 1. Schematic representation of the vigilin architecture: ovals indi- cate the KH motifs, linkes represent putative s-helical regions [10]. The five constructs expressed are indicated below. Numbers on the con- structs refer to the corresponing amino acid positions in te complete vigilin sequence from human. For simplicity the numbering adopted in the text refers to the starting of construct III so that for nstance Asn-7 coresponds to Asn-434 of the complete sequence. The sequence of construct I is explicitly shown: the sequence of the KH module is indicated in roman letters, while those of the flanking putative helices ar in italics.

Figure 3.
Fig. 3. (a) Survey o the NOE effects observed. In italics is the secondary structure prediction as obtained from the PredictProtein EMBL e-mail server [23] is reported together with the degree of confidence. The main classes of shor range contacts observed are shown togethe with the secondary chemical shifts (SCS) and protons which are solvent inacces- sible in solvent saturation transfer experiments (UP). A window of + 2 points as used to smooth the SCS data. (b) The three-strandedfl-sheet of the KH. Continuous lines identify observed nterstrand NOEs. A dotted line between Ile-14 and Ile-55 indicates that this effect could not be observed because these two amides are coincident. (c) Schematic reresentation of te secondary structure of the KH domain n the same orientation s in b.

The above figures are reproduced from the cited reference with permission from the Federation of European Biochemical Societies