PDBsum entry 3f31

Actin binding, structural protein

PDB id: 3f31

Contents

Protein chains

137 a.a. *

Waters ×206

* Residue conservation analysis

PDB id:

3f31

Name:

Actin binding, structural protein

Title:

Crystal structure of the n-terminal region of alphaii-spectrin tetramerization domain

Structure:

Spectrin alpha chain, brain. Chain: a, b. Synonym: spectrin, non-erythroid alpha chain, alpha-ii spectrin, fodrin alpha chain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: sptan1, spta2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.30Å R-factor: 0.220 R-free: 0.280

Authors:

S.Mehboob,B.D.Santarsiero,F.Long,M.Witek,L.W.Fung

Key ref:

S.Mehboob et al. (2010). Crystal structure of the nonerythroid alpha-spectrin tetramerization site reveals differences between erythroid and nonerythroid spectrin tetramer formation. J Biol Chem, 285, 14572-14584. PubMed id: 20228407

Date:

30-Oct-08 Release date: 13-Oct-09

Protein chains

Q13813  (SPTN1_HUMAN) -  Spectrin alpha chain, non-erythrocytic 1 from Homo sapiens

Seq: 2472 a.a.

Struc: 137 a.a.

J Biol Chem 285:14572-14584 (2010)

PubMed id: 20228407

Crystal structure of the nonerythroid alpha-spectrin tetramerization site reveals differences between erythroid and nonerythroid spectrin tetramer formation.

S.Mehboob, Y.Song, M.Witek, F.Long, B.D.Santarsiero, M.E.Johnson, L.W.Fung.

ABSTRACT

We have solved the crystal structure of a segment of nonerythroid alpha-spectrin (alphaII) consisting of the first 147 residues to a resolution of 2.3 A. We find that the structure of this segment is generally similar to a corresponding segment from erythroid alpha-spectrin (alphaI) but exhibits unique differences with functional significance. Specific features include the following: (i) an irregular and frayed first helix (Helix C'); (ii) a helical conformation in the junction region connecting Helix C' with the first structural domain (D1); (iii) a long A(1)B(1) loop in D1; and (iv) specific inter-helix hydrogen bonds/salt bridges that stabilize D1. Our findings suggest that the hydrogen bond networks contribute to structural domain stability, and thus rigidity, in alphaII, and the lack of such hydrogen bond networks in alphaI leads to flexibility in alphaI. We have previously shown the junction region connecting Helix C' to D1 to be unstructured in alphaI (Park, S., Caffrey, M. S., Johnson, M. E., and Fung, L. W. (2003) J. Biol. Chem. 278, 21837-21844) and now find it to be helical in alphaII, an important difference for alpha-spectrin association with beta-spectrin in forming tetramers. Homology modeling and molecular dynamics simulation studies of the structure of the tetramerization site, a triple helical bundle of partial domain helices, show that mutations in alpha-spectrin will affect Helix C' structural flexibility and/or the junction region conformation and may alter the equilibrium between spectrin dimers and tetramers in cells. Mutations leading to reduced levels of functional tetramers in cells may potentially lead to abnormal neuronal functions.