PDBsum entry 1i1j

Hormone/growth factor

PDB id: 1i1j

Contents

Protein chain

106 a.a. *

Waters ×212

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structure of melanoma inhibitory activity protein, A member of a recently identified family of secreted proteins.

Authors

J.C.Lougheed, J.M.Holton, T.Alber, J.F.Bazan, T.M.Handel.

Ref.

Proc Natl Acad Sci U S A, 2001, 98, 5515-5520. [DOI no: 10.1073/pnas.091601698]

PubMed id

11331761

Abstract

Melanoma inhibitory activity (MIA) is a 12-kDa protein that is secreted from both chondrocytes and malignant melanoma cells. MIA has been reported to have effects on cell growth and adhesion, and it may play a role in melanoma metastasis and cartilage development. We report the 1.4-A crystal structure of human MIA, which consists of an Src homology 3 (SH3)-like domain with N- and C-terminal extensions of about 20 aa. each. The N- and C-terminal extensions add additional structural elements to the SH3 domain, forming a previously undescribed fold. MIA is a representative of a recently identified family of proteins and is the first structure of a secreted protein with an SH3 subdomain. The structure also suggests a likely protein interaction site and suggests that, unlike conventional SH3 domains, MIA does not recognize polyproline helices.

Figure 1.
Fig. 1. The structure of melanoma inhibitory activity protein. -strands are in blue, regions lacking regular secondary structure are in green, 3[10] helices are in red, and disulfide bonds are in gold. (A) View of the two sheets that pack at right angles to each other. Sheet I is in front. 1 and 7 add onto sheet II of the SH3 -sandwich. The top of the barrel is toward the top of the page. (B) View looking into one end (mouth) of the barrel. The 30s-40s loop (analogous to the RT loop of SH3 domains) and the 60s-70s loop, flank one mouth of the barrel. The N-terminal residues preceding 1 and the C-terminal residues following 7 run along the outside face of sheet II. A and B are on the same scale.

Figure 4.
Fig. 4. Comparison of the SH3 polyproline helix binding site to the analogous region in MIA. (A) Superposition of the conserved residues in the polyproline helix binding site of Sem-5 (red) and the corresponding residues in MIA (blue). Four of six residues conserved in SH3 domains differ in MIA. Residue numbering corresponds to MIA. Residues listed in parentheses are those found in canonical SH3 domains. (B) View of the molecular surfaces of MIA (Left) and the Sem-5 SH3 domain (Right). The structure of Sem-5 is shown with its polyproline ligand bound. Sem-5 residues colored in red are those that make up a triad of conserved aromatic residues arranged approximately linearly on the molecular surface. The dissimilarity of the corresponding residues in MIA, F59, I83, and Q28 result in a much smoother molecular surface that most likely does not recognize polyproline helices.