Profile analysis: detection of distantly related proteins.

Gribskov, Michael; McLachlan, Anton; Eisenberg, David

doi:10.1073/pnas.84.13.4355

Cited by 1,163 publications

(669 citation statements)

References 26 publications

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“…PROFILEMAKE and related programs (GCG) were employed for profile analysis (Gribskov et al, 1987(Gribskov et al, , 1992. In the absence of structural information for the most divergent member of the flavodoxin family (flav-cloab), its sequence was aligned to a profile derived from the other flavodoxin sequences and then included in the family.…”

Section: Methodsmentioning

confidence: 99%

Six new candidate members of the α/β twisted open‐sheet family detected by sequence similarity to flavodoxin

Grandori

Carey

1994

Protein Science

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We discuss sequence conservation with reference to the known 3-dimensional structures of flavodoxins. Conserved sequence and hydrophobicity patterns, as well as residue-pair interaction potentials, strongly support the hypothesis that these proteins share the a//3 twisted open-sheet fold typical of flavodoxins, with an additional unit in the WrbA family. On the basis of the proposed structural homology, we discuss the details of the putative FMNbinding sites. Our analysis also suggests that the helix-turn-helix motif we identified previously in the C-terminal region of the WrbA family is unlikely to reflect a DNA-binding function of this new protein family.

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Section: Methodsmentioning

confidence: 99%

Six new candidate members of the α/β twisted open‐sheet family detected by sequence similarity to flavodoxin

Grandori

Carey

1994

Protein Science

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“…In the procedure going from the alignment to the profile, one wants to avoid bias toward sequences overrepresented in the alignment. In the currently used method for constructing the sequence profiles from an alignment, a weight can be given to each sequence (Gribskov et al, 1990), but there is no provision for assigning these weights automatically. This leads in practice to equal weights for all sequences.…”

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confidence: 99%

“…The most common implementation for the profile construction uses a logarithmic amino acid weighting locally at each position in the alignment (Gribskov et al, 1990) (see Methods). In addition to the alignment, the profile method also uses an amino acid substitution table (see Fig.…”

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confidence: 99%

Improving the sensitivity of the sequence profile method

1994

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The sequence profile method (Gribskov M, McLachlan AD, Eisenberg D, 1987, Proc Natl Acad Sci USA 844355-4358) is a powerful tool to detect distant relationships between amino acid sequences. A profile is a table of position-specific scores and gap penalties, providing a generalized description of a protein motif, which can be used for sequence alignments and database searches instead of an individual sequence. A sequence profile is derived from a multiple sequence alignment. We have found 2 ways to improve the sensitivity of sequence profiles: (1) Sequence weights: Usage of individual weights for each sequence avoids bias toward closely related sequences. These weights are automatically assigned based on the distance of the sequences using a published procedure (Sibbald PR, Argos P, 1990, JMolBiol216:813-818). (2) Amino acid substitution table: In addition to the alignment, the construction of a profile also needs an amino acid substitution

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“…A recent search of Protein Sequence Databases (SWISS, release 18.0 and NBRF/PIR, release 29.0) [22,23] identified only one other protein containing more than one region homologous to the WD-40 repeat, namely, ligninase, a lignin peroxidase, secreted by the fungus Phanerochaete chrysosporhmt [24,25]. It should be noted, however, that the second motif in ligninase displays a rather weak homology to the WD-40 consensus sequence.…”

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confidence: 99%

The WD‐40 repeat

1992

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An amino acid sequence motif, called the WD. 40 repeat, has b~en found as a repeat in a large variety of proteins that do not share any obvious functional properties. At present, the function of the repeated motif is not known for any of these proteins. Interestingly. recent experiments in yeast indicate that several proteins containing the WD-40 repeat are genetically associated with members of the TPR-family. a protein family that is characterized by the presence of another repeated motif of unknown function: the tetratrieopeptide repeat, it is conceivable that proteins containing the WD--t0 repeat interact physically with ~aenabers of the TPg-family via their respective repeated motifs.WD-40 repeat; G protein B-subunit; Protein family; TPR-gene familyMany proteins contain repeated motifs that may be considered as building blocks, representing structural elements or functional domains. The deduced amino acid sequence of the fl-subunit of heterotrimeric G-proteins revealed that, except for the first 50 N-terminal amino acids, the fl-subunit is comprised of 7 segments that show sequence similarity to each other and are arranged in tandem [1]. This repeated motif, referred to as the WD-40 repeat [2], is characterized by the presence of a number of amino acids, conserved not only with respect to the type of side chain, but also in their spacing. A similar motif has been found in several other proteins. Based on the presence of the WD-40 repeat, these proteins may constitute a WD-40 family.Members of the WD-40 family include: (i) the fl-subunit of guanine nucleotide regulatory proteins (G-proteins), a component of the heterotrimeric complex that transduces signals from transmembrane receptors to a variety of second messenger generating effectors [1,2]; (ii) STE4, a functional G-protein fl-subunit homologue in yeast (Saccharomyces cerevisiae), involved in a signal pathway that controls the response to mating pheromone [3]; (iii) CDC4, a component of the yeast nuclear cytoskeleton, required at the late Gj/S phase boundary of the cell cycle [4,5]; (iv) CDC20, a yeast gene product required for several microtubule-dependent processes at multiple stages in the cell cycle [6][7][8] [24,25]. It should be noted, however, that the second motif in ligninase displays a rather weak homology to the WD-40 consensus sequence. An alignment of all WD-40 repeats identified and a WD-40 consensus sequence based on this alignment are shown in Fig 1. The WD-40 repeat can be divided in 2 relatively conserved elements, A and B, spaced by regions variable in both sequence and length (Fig. I A)

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Profile analysis: detection of distantly related proteins.

Cited by 1,163 publications

References 26 publications

Six new candidate members of the α/β twisted open‐sheet family detected by sequence similarity to flavodoxin

Six new candidate members of the α/β twisted open‐sheet family detected by sequence similarity to flavodoxin

Improving the sensitivity of the sequence profile method

The WD‐40 repeat

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