PDBsum entry 1nct

Muscle protein

PDB id

1nct

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Contents

			Protein chain

					98 a.a. *

* Residue conservation analysis

PDB id:

1nct

Links

Name:

Muscle protein

Title:

Titin module m5, n-terminally extended, nmr

Structure:

Titin. Chain: a. Fragment: n-terminally extended module m5. Synonym: connectin, nextm5. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Tissue: cardiac muscle. Organelle: cytoplasma/sarcomere. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

1 models

Authors:

M.Pfuhl,A.Pastore

Key ref:

M.Pfuhl et al. (1997). When a module is also a domain: the rôle of the N terminus in the stability and the dynamics of immunoglobulin domains from titin. J Mol Biol, 265, 242-256. PubMed id: 9020985 DOI: 10.1006/jmbi.1996.0725

Date:

13-Aug-96

Release date:

08-Nov-96

PROCHECK

	Headers

	References

Protein chain

Q8WZ42 (TITIN_HUMAN) - Titin from Homo sapiens

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Seq: Struc:					34350 a.a. 98 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

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



		Enzyme reactions

Enzyme class:

E.C.2.7.11.1 - non-specific serine/threonine protein kinase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

1.	L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
2.	L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

L-seryl-[protein]	+	ATP	=	O-phospho-L-seryl-[protein]	+	ADP	+	H(+)

L-threonyl-[protein]	+	ATP	=	O-phospho-L-threonyl-[protein]	+	ADP	+	H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1006/jmbi.1996.0725	J Mol Biol 265:242-256 (1997)
PubMed id: 9020985

When a module is also a domain: the rôle of the N terminus in the stability and the dynamics of immunoglobulin domains from titin.
M.Pfuhl, S.Improta, A.S.Politou, A.Pastore.

ABSTRACT

In the course of a structural study of titin, a giant modular protein from muscle, we have reported that N-terminal extension of immunoglobulin-like (Ig-like) domains from titin stabilizes this fold. In order to investigate the structural basis of such an effect, we have solved the structure of NEXTM5, which has six amino acids added to the sequence of M5, a domain for which full structure determination has been previously achieved. In the present work, the structures and the dynamics of M5 and NEXTM5 are compared in the light of data collected for these and other titin domains. In NEXTM5, three out of the six added residues are structured and pack against the nearby BC and FG loops. As a consequence, three new backbone hydrogen bonds are formed with the B strand, extending the A strand by two residues and decreasing the exposed surface area of the loops. Additional contacts which involve the side-chains give rise to a remarkable pH dependence of the stability. Interestingly, no correlation is observed on the NMR time-scale between the overall dynamics of the extended domain and its increased stability. The most noticeable differences between the two constructs are localised around the N terminus, which becomes more rigid upon extension. Since a similar pattern of contacts is observed for other domains of the immunoglobulin I-set, our results are of general relevance for this protein family. Our work might also inspire a more rational approach to the investigation of domain boundaries and their influence on module stability.

Selected figure(s)



	Figure 2. Figure 2. Difference of the NEXTM5 − M5 chemical shifts of α (broken line) and amide protons (continuous line).		Figure 8. Figure 8. Pattern of hydrogen bonds for the β-sheet containing the N terminus in M5 (A), telokin (B) and I27 (C) with the relative variation of stability observed in M5 and I27 indicated below. The residues added upon extension of I27 and M5 are indicated in grey. The additional H-bonds formed in the two domains are indicated with broken lines. The melting point (t[m]) and the midpoint urea concentration ([U][1/2]) are expressed in deg.C and mol/l, respectively. The construct names are chosen to be consistent with previous publications.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21314639

S.Schröder, F.Fraternali, X.Quan, D.Scott, F.Qian, and M.Pfuhl (2011).
When a module is not a domain: the case of the REJ module and the redefinition of the architecture of polycystin-1.

Biochem J, 435, 651-660.

18982379

A.J.Ayme-Southgate, R.J.Southgate, R.A.Philipp, E.E.Sotka, and C.Kramp (2008).
The myofibrillar protein, projectin, is highly conserved across insect evolution except for its PEVK domain.

J Mol Evol, 67, 653-669.

19436439

S.Batey, A.A.Nickson, and J.Clarke (2008).
Studying the folding of multidomain proteins.

HFSP J, 2, 365-377.

16287100

A.Prasad, H.Zhao, J.M.Rutherford, N.Housley, C.Nichols, and S.Pedigo (2006).
Effect of linker segments on the stability of epithelial cadherin Domain 2.

Proteins, 62, 111-121.

15657118

M.M.Krishna, and S.W.Englander (2005).
The N-terminal to C-terminal motif in protein folding and function.

Proc Natl Acad Sci U S A, 102, 1053-1058.

14625307

D.Rünzler, C.Huber, D.Moll, G.Köhler, and M.Sára (2004).
Biophysical characterization of the entire bacterial surface layer protein SbsB and its two distinct functional domains.

J Biol Chem, 279, 5207-5215.

10819994

R.A.Atkinson, C.Joseph, F.Dal Piaz, L.Birolo, G.Stier, P.Pucci, and A.Pastore (2000).
Binding of alpha-actinin to titin: implications for Z-disk assembly.

Biochemistry, 39, 5255-5264.

10429210

J.Ruiz-Sanz, A.Simoncsits, I.Törö, S.Pongor, P.L.Mateo, and V.V.Filimonov (1999).
A thermodynamic study of the 434-repressor N-terminal domain and of its covalently linked dimers.

Eur J Biochem, 263, 246-253.

10359566

L.Vangelista, S.Laffer, R.Turek, H.Grönlund, W.R.Sperr, P.Valent, A.Pastore, and R.Valenta (1999).
The immunoglobulin-like modules Cepsilon3 and alpha2 are the minimal units necessary for human IgE-FcepsilonRI interaction.

J Clin Invest, 103, 1571-1578.

10467147

S.De Marino, M.A.Morelli, F.Fraternali, E.Tamborini, G.Musco, S.Vrtala, C.Dolecek, P.Arosio, R.Valenta, and A.Pastore (1999).
An immunoglobulin-like fold in a major plant allergen: the solution structure of Phl p 2 from timothy grass pollen.

Structure, 7, 943-952.

PDB code:

1bmw

9609701

S.J.Hamill, A.E.Meekhof, and J.Clarke (1998).
The effect of boundary selection on the stability and folding of the third fibronectin type III domain from human tenascin.

Biochemistry, 37, 8071-8079.

9204285

J.Heringa, and W.R.Taylor (1997).
Three-dimensional domain duplication, swapping and stealing.

Curr Opin Struct Biol, 7, 416-421.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.