The NfeD Protein Family and Its Conserved Gene Neighbours Throughout Prokaryotes: Functional Implications for Stomatin-Like Proteins

TY - JOUR

T1 - The NfeD Protein Family and Its Conserved Gene Neighbours Throughout Prokaryotes

T2 - Functional Implications for Stomatin-Like Proteins

AU - Green, Jasper B.

AU - Lower, Ryan P. J.

AU - Young, J. P. W.

N1 - 10.1007/s00239-009-9304-8

PY - 2009/12

Y1 - 2009/12

N2 - NfeD-like proteins are widely distributed throughout prokaryotes and are frequently associated with genes encoding stomatin-like proteins (slipins). Here, we reveal that the NfeD family is ancient and comprises three major groups: NfeD1a, NfeD1b and truncated NfeD1b. Members of each group are associated with one of four conserved gene partners, three of which have eukaryotic homologues that are membrane raft associated, namely stomatin, paraslipin (previously SLP-2) and flotillin. The first NfeD group (NfeD1b), comprises proteins of approximately 460-aa long that have three functional domains: an N-terminal protease, a middle membrane-spanning region and a soluble C-terminal region rich in beta-strands. The nfeD1b gene is adjacent to eoslipin in prokaryotic genomes except in Firmicutes and Deinococci, where yqfA replaces eoslipin. Proteins in the second major group (NfeD1a) are homologous to the C-terminus of NfeD1b which forms a beta-barrel-like domain, and their genes are associated with paraslipin. Using OrthoMCL clustering, we show that nfeD1b genes have become truncated on many independent occasions giving rise to the third major group. These short NfeD homologues frequently remain associated with their ancestral gene neighbour, resembling NfeD1a in structure, yet are much more related to full-length NfeD1b; we term these "truncated NfeD1b". These conserved associations suggest that NfeD proteins are dependent on gene partners for their function and that the site of interaction may lie within the C-terminal portion that is common to all NfeD homologues. Although NfeD homologues are confined to prokaryotes, this conserved association could represent an excellent system to study slipin and flotillin proteins.

AB - NfeD-like proteins are widely distributed throughout prokaryotes and are frequently associated with genes encoding stomatin-like proteins (slipins). Here, we reveal that the NfeD family is ancient and comprises three major groups: NfeD1a, NfeD1b and truncated NfeD1b. Members of each group are associated with one of four conserved gene partners, three of which have eukaryotic homologues that are membrane raft associated, namely stomatin, paraslipin (previously SLP-2) and flotillin. The first NfeD group (NfeD1b), comprises proteins of approximately 460-aa long that have three functional domains: an N-terminal protease, a middle membrane-spanning region and a soluble C-terminal region rich in beta-strands. The nfeD1b gene is adjacent to eoslipin in prokaryotic genomes except in Firmicutes and Deinococci, where yqfA replaces eoslipin. Proteins in the second major group (NfeD1a) are homologous to the C-terminus of NfeD1b which forms a beta-barrel-like domain, and their genes are associated with paraslipin. Using OrthoMCL clustering, we show that nfeD1b genes have become truncated on many independent occasions giving rise to the third major group. These short NfeD homologues frequently remain associated with their ancestral gene neighbour, resembling NfeD1a in structure, yet are much more related to full-length NfeD1b; we term these "truncated NfeD1b". These conserved associations suggest that NfeD proteins are dependent on gene partners for their function and that the site of interaction may lie within the C-terminal portion that is common to all NfeD homologues. Although NfeD homologues are confined to prokaryotes, this conserved association could represent an excellent system to study slipin and flotillin proteins.

KW - SPFH

KW - Eoslipin

KW - Paraslipin

KW - SLP-2

KW - Stomatin

KW - Flotillin

KW - NfeD

KW - YqfA

KW - YqeZ

KW - Phylogeny

KW - MULTIPLE SEQUENCE ALIGNMENT

KW - AMINO-ACID SUBSTITUTION

KW - SPFH DOMAIN

KW - PYROCOCCUS-HORIKOSHII

KW - MAXIMUM-LIKELIHOOD

KW - BACILLUS-SUBTILIS

KW - EVOLUTION

KW - HOMOLOG

KW - IDENTIFICATION

KW - FLOTILLIN

UR - http://www.scopus.com/inward/record.url?scp=72449165351&partnerID=8YFLogxK

U2 - 10.1007/s00239-009-9304-8

DO - 10.1007/s00239-009-9304-8

M3 - Article

SN - 0022-2844

VL - 69

SP - 657

EP - 667

JO - Journal of molecular evolution

JF - Journal of molecular evolution

IS - 6

ER -