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Sequence similarities of protein kinase substrates and inhibitors with immunoglobulins and model immunoglobulin homologue: Cell adhesion molecule from the living fossil spongeGeodia cydonium. Mapping of coherent database similarities and implications for evolution of CDR1 and hypermutation

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Abstract

Sequences of immunoglobulin (Ig) domains of adhesive molecule GSAMS from the living fossil spongeGeodia cydonium were compared with the important motif of peptide protein kinase substrates and inhibitors (PKSI), detail PKSI sequences, and a common template sequence, derived from structures determined previously. We found the site-restricted sequence similarities to these peptide sequences predominantly in the GSAM Ig1 domain of GSAMS in the domain region related to corresponding Ig similarities detected earlier. Additional sequence block-related analysis revealed the presence of CDR1-like segments within PKSI-related regions and resulted in the detection of increased numbers of hypermutation motifs just in the CDR1-like segment of GSAM Ig1 (GSAM(cdr1.1)). In the following database searches with PKSI-related regions and GSAM(cdr1.1) we looked for: (i) peptide similarities present in the context of Ig domains or related structures in a large range of species fromArchaea toVertebrata, and (ii) some special nucleotide similarities.

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Abbreviations

aa:

amino acid(s), amino acid residue(s)

AID:

activation-induced cytidine deaminase

ANCESTOR:

constructed ancestor-like template (see Table I)

“BF subset”:

subset of similar and equally located and long IgV segments forming sequence block and motif

CDR1, CDR2:

the first and the second hypervariable region of Ig variable domains, respectively

FMC, FMV:

final motifs derived with the aid of PKSI sequence blocks and block consensus sequences of: (i) all corresponding segments of constant Ig domains — FMC, (ii) equally located variable domain segments of the highest homology — FMV (Kubrychtet al. 2002)

GP:

terminal positions of the GSAMS segments similar to compared protein (marked by aa) or nucleotide (marked by N) sequences

GSAM:

fourGeodia cydonium adhesion molecules with or without receptor tyrosine kinase activity, molecules belonging to the immunoglobulin superfamily

GSAM(1), GSAM(2):

former GSAM segment derived in Table II

GSAM Ig1, GSAM Ig2:

two GSAM domains of high homology with immunoglobulins

GSAMS:

short form of adhesion molecule GSAM fromGeodia cydonium. For relationships between abbreviations and location of several GSAMS segments derived heresee Table VI

HLE :

horizontal length equivalent (see Chapter 2.2.6)

Ig:

immunoglobulin

IgV:

variable domain(s) of immunoglobulin(s)

IgVHS :

domain of high similarity with variable domains of immunoglobulins in agreement with the special limits for NCBI conserved domain search

IL:

interleukin

IP:

terminal positions of immunoglobulin segments of similar description to GP intervals

KBI:

“knowledge-based identities” — represent site-restricted sequence identities or alternative identities following from single triplet mutation analysis of sequence block(s) described here or in Kubrychtet al. (2002)

NCAM2:

neural cell adhesion molecule 2

OI:

oligonucleotide identity (-ies) between GSAM Ig1 segment (segments) and various mRNAs and genes

OX2:

CD200, membrane protein expressed by broad repertoire of cell types

PKCgs:

protein kinase C substrate derived from glycogen synthase

PK1 :

inhibitor of cAMP-dependent protein kinase

PKSI:

protein kinase peptide substrate(s) and or inhibitor(s)

PM:

primary derived motif

RMT:

regular template, related to the revised version of PM defined in Kubrychtet al. (2002). RMT reflects the sequence similarities in mixture block of sequences of the highest homology with PM

SNEM:

search for short/near exact matches, special BLAST search comparing short segments with database

TCR:

T-cell receptor(s)

ZIG-1:

“zwei” (two)-immunoglobulin-domain protein 1 — member of protein family possibly required for maintenance of ventral neural cord organization inCaenorhabditis elegans (Aurelioet al. 2002)

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Authors and Affiliations

  1. Center of Occupational Diseases, National Institute of Public Health, 100 42, Prague, Czechia

    J. Kubrycht & P. Souček

  2. Centro de Biologia Molecular e Engenharia, Universidade Estadual de Campinas, CEP 13083-970, Sao Paulo, Brazil

    J. Borecký

  3. Department of Membrane Transport Biophysics, Institute of Physiology, Academy of Sciences of the Czech Republic, 142 20, Prague, Czechia

    P. Ježek

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  1. J. Kubrycht
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Correspondence to J. Kubrycht.

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This study was supported by grant ofInternal Grant Agency of the Ministry of Public Health of the Czech Republic no. 6747-3.

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Kubrycht, J., Borecký, J., Souček, P. et al. Sequence similarities of protein kinase substrates and inhibitors with immunoglobulins and model immunoglobulin homologue: Cell adhesion molecule from the living fossil spongeGeodia cydonium. Mapping of coherent database similarities and implications for evolution of CDR1 and hypermutation. Folia Microbiol 49, 219–246 (2004). https://doi.org/10.1007/BF02931038

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