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KH domain

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KH domain
Structure of a KH domain from the human protein vigilin.
Identifiers
SymbolKH_1
PfamPF00013
Pfam clanCL0007
ECOD327.11.2
InterProIPR004088
SMARTKH
SCOP21vig / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1dt4​, 1dtj​, 1e3h​, 1e3p​, 1ec6​, 1j4w​, 1j5k​, 1k1g​, 1khm​, 1tua​, 1vig​, 1vih​, 1we8​, 1wvn​, 1x4m​, 1x4n​, 1ztg​, 1zzi​, 1zzj​, 1zzk​, 2axy​, 2ba0​, 2bl5​, 2cpq​, 2cte​, 2ctf​, 2ctj​, 2ctk​, 2ctl​, 2ctm​, 2fmr​, 2je6​, 2jea​, 2p2r​, 2pqu​, 2py9​, 2z0s
KH domain
Identifiers
SymbolKH_2
PfamPF07650
Pfam clanCL0007
ECOD327.11.1
InterProIPR004044
SMARTKH
PROSITEPS50823
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1ega​, 1fjg​, 1gix​, 1hnw​, 1hnx​, 1hnz​, 1hr0​, 1i94​, 1i95​, 1i96​, 1i97​, 1ibk​, 1ibl​, 1ibm​, 1j5e​, 1n32​, 1n33​, 1n34​, 1n36​, 1vs5​, 1vs7​, 1wf3​, 1wh9​, 1xmo​, 1xmq​, 1xnq​, 1xnr​, 1yl4​, 2avy​, 2aw7​, 2b64​, 2b9m​, 2b9o​, 2e5l​, 2f4v​, 2hgi​, 2hgp​, 2hgr​, 2hhh​, 2i2p​, 2i2u​, 2j00​, 2j02​, 2ow8​, 2qal​, 2qan​, 2qb9​, 2qbb​, 2qbd​, 2qbf​, 2qbh​, 2qbj​, 2qnh​, 2qou​, 2qow​, 2qoy​, 2qp0​, 2uu9​, 2uua​, 2uub​, 2uuc​, 2uxb​, 2uxc​, 2uxd​, 2v46​, 2v48​, 2vho​, 2vhp​, 2vqe​, 2vqf​, 2z4k​, 2z4m​, 3d5a​, 3d5c​, 3df1​, 3df3​, 3f1e​, 3f1g

The K Homology (KH) domain is a protein domain that was first identified in the human heterogeneous nuclear ribonucleoprotein (hnRNP) K. An evolutionarily conserved sequence of around 70 amino acids, the KH domain is present in a wide variety of nucleic acid-binding proteins. The KH domain binds RNA, and can function in RNA recognition.[1] It is found in multiple copies in several proteins, where they can function cooperatively or independently. For example, in the AU-rich element RNA-binding protein KSRP, which has 4 KH domains, KH domains 3 and 4 behave as independent binding modules to interact with different regions of the AU-rich RNA targets.[1] The solution structure of the first KH domain of FMR1 and of the C-terminal KH domain of hnRNP K determined by nuclear magnetic resonance (NMR) revealed a beta-alpha-alpha-beta-beta-alpha structure.[2][3] Autoantibodies to NOVA1, a KH domain protein, cause paraneoplastic opsoclonus ataxia. The KH domain is found at the N-terminus of the ribosomal protein S3. This domain is unusual in that it has a different fold compared to the normal KH domain.[4]

Nucleic acid binding

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KH domains bind to either RNA or single stranded DNA. The nucleic acid is bound in an extended conformation across one side of the domain. The binding occurs in a cleft formed between alpha helix 1, alpha helix 2 the GXXG loop (contains a highly conserved sequence motif) and the variable loop.[5] The binding cleft is hydrophobic in nature with a variety of additional protein specific interactions to stabilise the complex. Valverde and colleagues note that, "Nucleic acid base-to-protein aromatic side chain stacking interactions which are prevalent in other types of single stranded nucleic acid binding motifs, are notably absent in KH domain nucleic acid recognition".[5]

Structural groups

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The two types of KH domain.

Structurally there are two different types of KH domains identified by Grishin which are called type I and type II.[4] The type I domains are mainly found in eukaryotic proteins, while the type II domains are predominantly found in prokaryotes. While both types share a minimal consensus sequence motif they have different structural folds. The type I KH domains have a three stranded beta-sheet where all three strands are anti-parallel. In the type II domain two of the three beta strands are in a parallel orientation. While type I domains are usually found in multiple copies within proteins, the type II are typically found in a single copy per protein.[5]

Human proteins containing this domain

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AKAP1; ANKHD1; ANKRD17; ASCC1; BICC1; DDX43; DDX53; DPPA5; ERAL1; FMR1; FUBP1; FUBP3; FXR1; FXR2; GLD1; HDLBP; HNRPK; IGF2BP1; IGF2BP2; IGF2BP3; KHDRBS1; KHDRBS2; KHDRBS3; KHSRP; KRR1; MEX3A; MEX3B; MEX3C; MEX3D; NOVA1; NOVA2; PCBP1; PCBP2; PCBP3; PCBP4; PNO1; PNPT1; QKI; SF1; TDRKH;

References

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  1. ^ a b García-Mayoral MF, Hollingworth D, Masino L, et al. (April 2007). "The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation" (PDF). Structure. 15 (4): 485–98. doi:10.1016/j.str.2007.03.006. PMID 17437720.
  2. ^ Musco G, Kharrat A, Stier G, et al. (September 1997). "The solution structure of the first KH domain of FMR1, the protein responsible for the fragile X syndrome". Nat. Struct. Biol. 4 (9): 712–6. doi:10.1038/nsb0997-712. PMID 9302998. S2CID 11166126.
  3. ^ Baber JL, Libutti D, Levens D, Tjandra N (June 1999). "High precision solution structure of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K, a c-myc transcription factor". J. Mol. Biol. 289 (4): 949–62. doi:10.1006/jmbi.1999.2818. PMID 10369774.
  4. ^ a b Grishin NV (February 2001). "KH domain: one motif, two folds". Nucleic Acids Res. 29 (3): 638–43. doi:10.1093/nar/29.3.638. PMC 30387. PMID 11160884.
  5. ^ a b c Valverde R, Edwards L, Regan L (June 2008). "Structure and function of KH domains". FEBS J. 275 (11): 2712–26. doi:10.1111/j.1742-4658.2008.06411.x. PMID 18422648.
This article incorporates text from the public domain Pfam and InterPro: IPR004088