Structural organization of the major autolysin from Streptococcus pneumoniae.


Abstract

LytA amidase is the best known bacterial autolysin. It breaks down the N-acetylmuramoyl-L-alanine bonds in the peptidoglycan backbone of Streptococcus pneumoniae and requires the presence of choline residues in the cell-wall teichoic acids for activity. Genetic experiments have supported the hypothesis that its 36-kDa chain has evolved by the fusion of two independent modules: the NH2-terminal module, responsible for the catalytic activity, and the COOH-terminal module, involved in the attachment to the cell wall. The structural organization of LytA amidase and of its isolated COOH-terminal module (C-LytA) and the variations induced by choline binding have been examined by differential scanning calorimetry and analytical ultracentrifugation. Deconvolution of calorimetric curves have revealed a folding of the polypeptide chain in several independent or quasi-independent cooperative domains. Elementary transitions in C-LytA are close but not identical to those assigned to the COOH-terminal module in the complete amidase, particularly in the absence of choline. These results indicate that the NH2-terminal region of the protein is important for attaining the native tertiary fold of the COOH terminus. Analytical ultracentrifugation studies have shown that LytA exhibits a monomer <--> dimer association equilibrium, through the COOH-terminal part of the molecule. Dimerization is regulated by choline interaction and involves the preferential binding of two molecules of choline per dimer. Sedimentation velocity experiments give frictional ratios of 1.1 for C-LytA monomer and 1.4 for C-LytA and LytA dimers; values that deviated from that of globular rigid particles. When considered together, present results give evidence that LytA amidase might be described as an elongated molecule consisting of at least four domains per subunit (two per module) designated here in as N1, N2, C1, and C2. Intersubunit cooperative interactions through the C2 domain in LytA dimer occur under all experimental conditions, while C-LytA requires the saturation of low affinity choline binding sites. The relevance of the structural features deduced here for LytA amidase is examined in connection with its biological function. Study holds ProTherm entries: 5245, 5246, 5247, 5248, 5249, 5250, 5251 Extra Details: choline residues; activity; structural organization;,calorimetric curves; cooperative domains; structural features

Submission Details

ID: p9ryt6Qs3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:29 p.m.

Version: 1

Publication Details
Usobiaga P;Medrano FJ;Gasset M;Garciá JL;Saiz JL;Rivas G;Laynez J;Menéndez M,J. Biol. Chem. (1996) Structural organization of the major autolysin from Streptococcus pneumoniae. PMID:8636107
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
5CTV 2016-06-15 1.05 Catalytic domain of LytA, the major autolysin of Streptococcus pneumoniae, (C60A, H133A, C136A mutant) complexed with peptidoglycan fragment
4IVV 2014-01-29 1.05 Catalytic amidase domain of the major autolysin LytA from Streptococcus pneumaniae
4X36 2015-05-27 2.1 Crystal structure of the autolysin LytA from Streptococcus pneumoniae TIGR4
1H8G 2002-01-31 2.4 C-terminal domain of the major autolysin (C-LytA) from Streptococcus pneumoniae
2BML 2005-03-30 2.6 Ofloxacin-like antibiotics inhibit pneumococcal cell wall degrading virulence factors
1HCX 2001-11-29 2.6 Choline binding domain of the major autolysin (C-LytA) from Streptococcus pneumoniae
1GVM 2002-08-01 2.8 CHOLINE BINDING DOMAIN OF THE MAJOR AUTOLYSIN (C-LYTA) FROM STREPTOCOCCUS PNEUMONIAE

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Autolysin P06653 ALYS_STRPN