KH domain: one motif, two folds.
The K homology (KH) module is a widespread RNA-binding motif that has been detected by sequence similarity searches in such proteins as heterogeneous nuclear ribonucleoprotein K (hnRNP K) and ribosomal protein S3. Analysis of spatial structures of KH domains in hnRNP K and S3 reveals that they are topologically dissimilar and thus belong to different protein folds. Thus KH motif proteins provide a rare example of protein domains that share significant sequence similarity in the motif regions but possess globally distinct structures. The two distinct topologies might have arisen from an ancestral KH motif protein by N- and C-terminal extensions, or one of the existing topologies may have evolved from the other by extension, displacement and deletion. C-terminal extension (deletion) requires ss-sheet rearrangement through the insertion (removal) of a ss-strand in a manner similar to that observed in serine protease inhibitors serpins. Current analysis offers a new look on how proteins can change fold in the course of evolution.
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Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9050, USA. grishin@chop.swmed.edu
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D016208:Databases, Factual; D019143:Evolution, Molecular; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D012261:Ribonucleoproteins / Q000737:chemistry / Q000235:genetics*; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D012269:Ribosomal Proteins; C044152:ribosomal protein S3; C072074:HNRNPK protein, human; C075197:high density lipoprotein binding protein