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Methyl-Lysine Recognition by Ankyrin-Repeat Proteins

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Histone Recognition

Abstract

The ankyrin repeats (ANKs) of the methyltransferases G9a and GLP bind methyllysine (meK) in a surface aromatic cage. Binding the methylation product with the very same polypeptide that generates it seems essential for some G9a/GLP functions, but it is dispensable for others. We first consider the structure of ANKs, particularly to illustrate that different binding modes can exist on the same scaffold and to facilitate the search for other meK-binding ANKs. Huntingtin (HTT)-interacting protein-14 (HIP14) was predicted based on conservation of key cage residues to also have a surface aromatic cage. This prediction has been confirmed, but the HIP14-binding partner remains elusive. HIP14 interacts with HTT through its ANKs. HTT directly binds a methyltransferase and manifests improper patterns of post-translational modification in Huntington’s disease. We have extended the search for other ANKs with meK-binding potential, and we present our results.

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  1. Department of Physical Sciences, Eastern Connecticut State University, 83 Windham Street, Willimantic, CT, 06226, USA

    Robert E. Collins

  2. Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road NE, Atlanta, GA, 30322, USA

    Xiaodong Cheng

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  1. Robert E. Collins
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  2. Xiaodong Cheng
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Correspondence to Robert E. Collins .

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Editors and Affiliations

  1. Department of Structural & Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

    Ming-Ming Zhou

Appendix: Abbreviations Used in Table  5.1

Appendix: Abbreviations Used in Table  5.1

CLIP4 :

CAP–Gly domain-containing linker protein 4; restin-like protein 2

GABP2 :

GA-binding protein subunit beta-2

GABP1 :

GA-binding protein subunit beta-1; transcription factor E4TF1-47

ANR55 :

Ankyrin-repeat domain-containing protein 55

EHMT2 :

Euchromatic histone-lysine N-methyltransferase 2, G9a, KMT1C

EHMT1 :

Euchromatic histone-lysine N-methyltransferase 1; G9a-like protein; KMT1D

ASB8 :

Ankyrin repeats and Socs box 8

ASB7 :

Ankyrin repeat and Socs box 8

ANKMY :

Ankyrin-repeat and MYND domain-containing protein 2

ANR50 :

Ankyrin-repeat domain-containing protein 50

ANS1B :

Ankyrin-repeat and sterile alpha motif domain-containing protein 1B; amyloid-beta protein intracellular domain-associated protein (AIDA-1)

CSK1l :

Caskin-1 (CASK-interacting protein 1)

BTBDB :

Ankyrin-repeat and BTB/POZ domain-containing protein; BTBD11

ANKS3 :

Ankyrin-repeat and SAM domain-containing protein 3

TNI3   K :

Serine/threonine-protein kinase TNNI3K, cardiac ankyrin-repeat kinase (CARK)(.1and .2 designate the first and second cage containing ankyrin repeats of the same protein)

TANC1 :

TPR domain, ankyrin-repeat, and coiled-coil-containing 1, rolling pebbles homolog B

TANC2 :

TPR domain, ankyrin-repeat, and coiled-coil-containing 2 (J3KRP9)

TRPA1 :

Transient receptor potential cation channel subfamily A member 1

USH1G :

Usher syndrome type-1G protein; scaffold protein containing ankyrin repeats and SAM domain (SANS)

HARP :

Ankyrin-repeat and SAM domain-containing protein 4B; harmonin-interacting ankyrin-repeat-containing protein

KRIT1 :

Krev interaction trapped protein 1, cerebral cavernous malformations 1 protein

ASB6 :

Ankyrin-repeat and SOCS box protein 6

SARP2 :

Several ankyrin-repeat protein transcript variant 2

ANR10 :

Ankyrin-repeat domain-containing protein 10

TNKS1 :

Tankyrase-1, ADP-ribosyltransferase diphtheria toxin-like 5, Poly [ADP-ribose] polymerase 5A

KIDINS220L :

highly similar to kinase D-interacting substance of 220   kDa

HIP14 :

Huntingtin-interacting protein 14, palmitoyltransferase ZDHHC

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Collins, R.E., Cheng, X. (2015). Methyl-Lysine Recognition by Ankyrin-Repeat Proteins . In: Zhou, MM. (eds) Histone Recognition. Springer, Cham. https://doi.org/10.1007/978-3-319-18102-8_5

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