Complete amino acid sequence of streptococcal PepM49 protein, a nephritis-associated serotype. Conserved conformational design among sequentially distinct M protein serotypes.

K M Khandke,T Fairwell,A S Acharya,B L Trus,B N Manjula

doi:10.1016/s0021-9258(18)60681-7

Abstract

The complete amino acid sequence of PepM49, a peptic fragment of the group A streptococcal type 49 M protein, the antiphagocytic cell surface molecule of the bacteria, is described. This fragment retains the opsonic antibody epitope of the native molecule. The sequence of PepM49, as determined by automated Edman degradations of the uncleaved molecule, and its tryptic and chymotryptic peptides, consists of a total of 143 residues (Mr = 17,187). PepM49, a nephritis-associated M protein serotype, exhibits significant internal homology in its sequence. However, identical sequence repeats of the kind seen in the rheumatic fever-associated serotypes M5, M6, and M24, are absent in PepM49. PepM49 exhibits varying degrees of homology with the M5, M6, and M24 proteins, which is consistent with the existence of variable and conserved regions in the M protein molecule. Predictive analysis as well as CD measurements revealed a high propensity of the PepM49 molecule to assume an alpha-helical conformation. Furthermore, a heptad periodicity of the nonpolar residues, a characteristic of alpha-helical coiled-coil proteins, extends over the entire length of the PepM49 protein. The differences in the nonpolar residue distribution divide the PepM49 sequence into three distinct domains, similar to those seen earlier in the M5 and M6 proteins. Together, these studies establish a conserved conformational design for the sequentially diverse M protein serotypes. However, the pattern of heptad periodicity in the PepM49 protein is quite distinct from that present in the PepM5 and M6 proteins, suggesting distinct differences in structural features among conformationally similar M protein serotypes. This may have relevance to the pathological differences associated with these M protein serotypes.

Highlights

The complete amino acid sequence of PepM49, a [1,2,3,4,5,6]
The differences in the studies have revealed that regions within the COOH-terminal nonpolar residue distribution divide the PepM49 se- half of the M molecule are conserved among many M seroquence into three distinct domains, similar to those types and those inthe NH,terminal region are more variable, seen earlier in thMe5 and M6 proteins
In thisreport we present the Sequence Repeats in PepM49-A dot matrix analysis [35] complete amino acid sequence of PepM49, a peptic fragment of the PepM49 sequence revealed significant internal homolof the type 49 M protein that retains the opsonic antibody ogies which are localized in essentially two distinct regions epitope of the native molecule

Summary

MATERIALS AND METHODS

Amino Acid Sequence of PepM49"The complete amino acid sequence of PepM49 together with the dataleading to its. In thisreport we present the Sequence Repeats in PepM49-A dot matrix analysis [35] complete amino acid sequence of PepM49, a peptic fragment of the PepM49 sequence revealed significant internal homolof the type 49 M protein that retains the opsonic antibody ogies which are localized in essentially two distinct regions epitope of the native molecule. The homologies in the NH2- PepM49 exhibited 33% identity with segment 156-304 of M6 terminal region (region A) are limited Those in the (149-residueoverlap) (Fig. 4C).More significant are the idenregion COOH-terminal to this (region B) are more extensive tities in the last 30 residues within this stretch. '1 was observed between segment 1-103 of PepM49 and 97-196 of PepM5 (Fig. a),whereas segment 107-132 of PepM49 showed 38% identity with peptide CB3 of the M24 protein (26-residue overlap) (Fig. 4B), and the complete sequence of.

58 Gin Val Ala Ala Asp Lys H i s

Findings

DISCUSSION