Independent movement, dimerization and stability of tandem repeats of chicken brain alpha-spectrin.


Abstract

Previous X-ray crystal structures have shown that linkers of five amino acid residues connecting pairs of chicken brain alpha-spectrin and human erythroid beta-spectrin repeats can undergo bending without losing their alpha-helical structure. To test whether bending at one linker can influence bending at an adjacent linker, the structures of two and three repeat fragments of chicken brain alpha-spectrin have been determined by X-ray crystallography. The structure of the three-repeat fragment clearly shows that bending at one linker can occur independently of bending at an adjacent linker. This observation increases the possible trajectories of modeled chains of spectrin repeats. Furthermore, the three-repeat molecule crystallized as an antiparallel dimer with a significantly smaller buried interfacial area than that of alpha-actinin, a spectrin-related molecule, but large enough and of a type indicating biological specificity. Comparison of the structures of the spectrin and alpha-actinin dimers supports weak association of the former, which could not be detected by analytical ultracentrifugation, versus strong association of the latter, which has been observed by others. To correlate features of the structure with solution properties and to test a previous model of stable spectrin and dystrophin repeats, the number of inter-helical interactions in each repeat of several spectrin structures were counted and compared to their thermal stabilities. Inter-helical interactions, but not all interactions, increased in parallel with measured thermal stabilities of each repeat and in agreement with the thermal stabilities of two and three repeats and also partial repeats of spectrin. Study holds ProTherm entries: 18184, 18185, 18186, 18187, 18188 Extra Details: Repeat 15 (residues 1665-1770) spectrin; crystal structure; dimer conformation; flexibility; thermodynamic folding stability

Submission Details

ID: 5CE2uE57

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:50 p.m.

Version: 1

Publication Details
Kusunoki H;Minasov G;Macdonald RI;Mondragón A,J. Mol. Biol. (2004) Independent movement, dimerization and stability of tandem repeats of chicken brain alpha-spectrin. PMID:15522301
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
2JMA 2007-04-24 R21A Spc-SH3:P41 complex
2JM9 2007-04-24 R21A Spc-SH3 bound
2KR3 2010-09-15 Solution structure of SHA-D
2KXD 2011-04-20 The structure of SH3-F2
2ROT 2009-04-28 Structure of chimeric variant of SH3 domain- SHH
1M8M 2002-11-20 SOLID-STATE MAS NMR STRUCTURE OF THE A-SPECTRIN SH3 DOMAIN
2LJ3 2011-12-07 PFBD: High-throughput Strategy of Backbone fold Determination for small well-folded proteins in less than a day
1AJ3 1997-07-07 SOLUTION STRUCTURE OF THE SPECTRIN REPEAT, NMR, 20 STRUCTURES
1AEY 1997-05-15 ALPHA-SPECTRIN SRC HOMOLOGY 3 DOMAIN, SOLUTION NMR, 15 STRUCTURES
2JM8 2007-04-24 R21A Spc-SH3 free
2RMO 2008-09-30 Solution structure of alpha-spectrin_SH3-bergerac from Chicken
2JMC 2007-04-24 Chimer between Spc-SH3 and P41
3NGP 2010-09-08 1.08 High resolution structure of alpha-spectrin SH3 domain mutant with a redesigned core
3M0R 2011-01-19 1.1 Crystal Structure of the R21D mutant of alpha-spectrin SH3 domain. Crystal obtained in ammonium sulphate at pH 6.
3M0U 2011-01-19 1.1 Crystal Structure of the R21D mutant of alpha-spectrin SH3 domain. Hexagonal crystal obtained in sodium formate at pH 6.5.
1G2B 2000-11-01 1.12 ALPHA-SPECTRIN SRC HOMOLOGY 3 DOMAIN, CIRCULAR PERMUTANT, CUT AT N47-D48
5IHK 2017-03-29 1.35 Crystal Structure of the alpha spectrin SH3 domain mutant N47A
5FWC 2016-12-28 1.4 Human Spectrin SH3 domain D48G, E7A, K60A
3I9Q 2009-12-15 1.45 Crystal Structure of the triple mutant S19G-P20D-R21S of alpha spectrin SH3 domain
5IHI 2017-03-29 1.45 Crystal Structure of the alpha spectrin SH3 domain double mutant V46G-D48G
1U06 2005-01-13 1.49 crystal structure of chicken alpha-spectrin SH3 domain
5IHN 2017-03-29 1.5 Crystal Structure of the alpha spectrin SH3 domain mutant N47G
5FWB 2016-12-28 1.5 Human Spectrin SH3 domain D48G, E7F, K60F
4F17 2013-05-08 1.55 Crystal Structure of the alpha spectrin SH3 domain at pH 9
5FW9 2016-12-28 1.55 Human Spectrin SH3 domain D48G, E7Y, K60Y
3M0S 2011-01-19 1.6 Crystal Structure of the R21D mutant of alpha-spectrin SH3 domain. Crystal obtained in ammonium sulphate at pH 7
2F2X 2006-10-31 1.6 alpha-spectrin SH3 domain R21G mutant
2F2W 2006-10-31 1.7 alpha-spectrin SH3 domain R21A mutant
3M0T 2011-01-19 1.7 Crystal Structure of the R21D mutant of alpha-spectrin SH3 domain. Crystal obtained in ammonium sulphate at pH 9.
3THK 2011-11-23 1.7 Structure of SH3 chimera with a type II ligand linked to the chain C-terminal
3M0Q 2011-01-19 1.75 Crystal Structure of the R21D mutant of alpha-spectrin SH3 domain. Crystal obtained in ammonium sulphate at pH 5.
1PWT 1999-05-11 1.77 THERMODYNAMIC ANALYSIS OF ALPHA-SPECTRIN SH3 AND TWO OF ITS CIRCULAR PERMUTANTS WITH DIFFERENT LOOP LENGTHS: DISCERNING THE REASONS FOR RAPID FOLDING IN PROTEINS
1TUD 1996-08-01 1.77 ALPHA-SPECTRIN SRC HOMOLOGY 3 DOMAIN, CIRCULAR PERMUTANT, CUT AT N47-D48
1QKX 2000-12-15 1.8 Alpha-spectrin Src Homology 3 domain, N47A mutant in the distal loop.
1SHG 1993-10-31 1.8 CRYSTAL STRUCTURE OF A SRC-HOMOLOGY 3 (SH3) DOMAIN
2NUZ 2007-05-15 1.85 crystal structure of alpha spectrin SH3 domain measured at room temperature
2F2V 2006-10-31 1.85 alpha-spectrin SH3 domain A56G mutant
2OAW 2008-04-08 1.9 Structure of SHH variant of 'Bergerac' chimera of spectrin SH3
4F16 2013-05-08 1.93 Crystal Structure of the alpha spectrin SH3 domain at pH 5
1HD3 2001-11-01 1.98 A-SPECTRIN SH3 DOMAIN F52Y MUTANT
1QKW 2000-08-18 2.0 Alpha-spectrin Src Homology 3 domain, N47G mutant in the distal loop.
1CUN 1999-10-06 2.0 CRYSTAL STRUCTURE OF REPEATS 16 AND 17 OF CHICKEN BRAIN ALPHA SPECTRIN
1U5P 2004-10-19 2.0 Crystal Structure of Repeats 15 and 16 of Chicken Brain Alpha Spectrin
1E6H 2002-05-23 2.01 A-SPECTRIN SH3 DOMAIN A11V, M25I, V44I, V58L MUTANTS
1BK2 1999-02-16 2.01 A-SPECTRIN SH3 DOMAIN D48G MUTANT
1TUC 1996-08-01 2.02 ALPHA-SPECTRIN SRC HOMOLOGY 3 DOMAIN, CIRCULAR PERMUTANT, CUT AT S19-P20
1NEG 2003-01-14 2.3 Crystal Structure Analysis of N-and C-terminal labeled SH3-domain of alpha-Chicken Spectrin
1E6G 2002-05-23 2.3 A-SPECTRIN SH3 DOMAIN A11V, V23L, M25I, V53I, V58L MUTANT
3FB2 2008-11-25 2.3 Crystal structure of the human brain alpha spectrin repeats 15 and 16. Northeast Structural Genomics Consortium target HR5563a.
3F31 2009-10-13 2.3 Crystal Structure of the N-terminal region of AlphaII-spectrin Tetramerization Domain
2FOT 2006-09-05 2.45 Crystal structure of the complex between calmodulin and alphaII-spectrin
1U4Q 2004-10-19 2.5 Crystal Structure of Repeats 15, 16 and 17 of Chicken Brain Alpha Spectrin
2CDT 2007-02-20 2.54 alpha-SPECTRIN SH3 DOMAIN A56S MUTANT
3M0P 2011-01-19 2.6 Crystal Structure of the R21D mutant of alpha-spectrin SH3 domain. Crystal obtained in ammonium sulphate at pH 4.
1UUE 2004-02-19 2.6 a-SPECTRIN SH3 DOMAIN (V44T, D48G MUTANT)
1H8K 2002-05-23 2.7 A-SPECTRIN SH3 DOMAIN A11V, V23L, M25V, V53I, V58L MUTANT
1E7O 2003-05-21 3.2 A-SPECTRIN SH3 DOMAIN A11V, V23L, M25V, V44I, V58L MUTATIONS
5M6S 2017-01-11 4.8 folding intermediate of spectrin R16

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Spectrin alpha chain, non-erythrocytic 1 P16086 SPTN1_RAT
100.0 Spectrin alpha chain, non-erythrocytic 1 P16546 SPTN1_MOUSE
100.0 Spectrin alpha chain, non-erythrocytic 1 Q13813 SPTN1_HUMAN
100.0 Spectrin alpha chain, non-erythrocytic 1 P07751 SPTN1_CHICK