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6c9d

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Revision as of 09:57, 4 December 2019

Crystal structure of KA1-autoinhibited MARK1 kinase

Structural highlights

6c9d is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	MARK1, KIAA1477, MARK (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MARK1_HUMAN] Note=Genetic variations in MARK1 may be associated with susceptibility to autism. MARK1 is overexpressed in the prefrontal cortex of patients with autism and causes changes in the function of cortical dendrites.

Function

[MARK1_HUMAN] Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2, MAP4 and MAPT/TAU. Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3).^[1] ^[2]

Publication Abstract from PubMed

The kinase associated-1 (KA1) domain is found at the C-terminus of multiple Ser/Thr protein kinases from yeast to humans, and has been assigned autoinhibitory, membrane-binding, and substrate-targeting roles. Here, we report the crystal structure of the MARK1 kinase/UBA domain bound to its autoinhibitory KA1 domain, revealing an unexpected interface at the alphaD helix and contacts with both the N- and C-lobes of the kinase domain. We confirm the binding interface location in kinetic studies of variants mutated on the kinase domain surface. Together with other MARK kinase structures, the data implicate that the KA1 domain blocks peptide substrate binding. The structure highlights the kinase-specific autoinhibitory binding modes of different KA1 domains, and provides potential new avenues by which to intervene therapeutically in Alzheimer's disease and cancers in which MARK1 or related kinases are implicated.

Structural Basis for MARK1 Kinase Autoinhibition by Its KA1 Domain.,Emptage RP, Lemmon MA, Ferguson KM, Marmorstein R Structure. 2018 Aug 7;26(8):1137-1143.e3. doi: 10.1016/j.str.2018.05.008. Epub, 2018 Jun 28. PMID:30099988^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sun TQ, Lu B, Feng JJ, Reinhard C, Jan YN, Fantl WJ, Williams LT. PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling. Nat Cell Biol. 2001 Jul;3(7):628-36. PMID:11433294 doi:10.1038/35083016
↑ Kojima Y, Miyoshi H, Clevers HC, Oshima M, Aoki M, Taketo MM. Suppression of tubulin polymerization by the LKB1-microtubule-associated protein/microtubule affinity-regulating kinase signaling. J Biol Chem. 2007 Aug 10;282(32):23532-40. Epub 2007 Jun 15. PMID:17573348 doi:10.1074/jbc.M700590200
↑ Emptage RP, Lemmon MA, Ferguson KM, Marmorstein R. Structural Basis for MARK1 Kinase Autoinhibition by Its KA1 Domain. Structure. 2018 Aug 7;26(8):1137-1143.e3. doi: 10.1016/j.str.2018.05.008. Epub, 2018 Jun 28. PMID:30099988 doi:http://dx.doi.org/10.1016/j.str.2018.05.008

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6c9d"

@@ Line 1: / Line 1: @@
 ==Crystal structure of KA1-autoinhibited MARK1 kinase==
-<StructureSection load='6c9d' size='340' side='right' caption='[[6c9d]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='6c9d' size='340' side='right'caption='[[6c9d]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6c9d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C9D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C9D FirstGlance]. <br>
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 6c9d" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
 == References ==
 <references/>
@@ Line 25: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Emptage, R P]]
 [[Category: Marmorstein, R]]

6c9d

From Proteopedia

Revision as of 09:57, 4 December 2019

Crystal structure of KA1-autoinhibited MARK1 kinase

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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