Inositol polyphosphate 5-phosphatase OCRL: Difference between revisions
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== OCRL1 == | == OCRL1 == | ||
=== Domains === | === Domains === | ||
The 901 amino acid long OCRL1 is composed of multiple domains which enable it to interact with various partners. OCRL1 consists of an N-terminus '''pleckstrin homology (PH)''' domain without a basic patch required for phosphoinositide recognition and binding. On the other hand, it contains a loop outside of the domain fold that is involved in OCRL1 recruitment to endocytic clathrin-coated pits. <ref name="PH">PMID: 19536138</ref> | The 901 amino acid long '''OCRL1''' or '''Lowe oculocerebronal syndrome protein''' or '''Inositol polyphosphate 5-phosphatase OCRL''' is composed of multiple domains which enable it to interact with various partners. OCRL1 consists of an N-terminus '''pleckstrin homology (PH)''' domain without a basic patch required for phosphoinositide recognition and binding. On the other hand, it contains a loop outside of the domain fold that is involved in OCRL1 recruitment to endocytic clathrin-coated pits. <ref name="PH">PMID: 19536138</ref> | ||
PH domain is followed by one of the major conserved domains of OCRL1 which is a central '''5-phosphatase (5P) domain''', in which two characteristic motifs are present (WXGDXN(F/Y)R and P(A/S)W(C/T)DRIL separated by 60-75 amino acids (AAs)). These play an important role in both substrate binding and catalysis.<ref name="OCRL">PMID: 16101675</ref> This domain has a Dnase I-like fold. <ref name="IP5">PMID: 22381590</ref> | PH domain is followed by one of the major conserved domains of OCRL1 which is a central '''5-phosphatase (5P) domain''', in which two characteristic motifs are present (WXGDXN(F/Y)R and P(A/S)W(C/T)DRIL separated by 60-75 amino acids (AAs)). These play an important role in both substrate binding and catalysis.<ref name="OCRL">PMID: 16101675</ref> This domain has a Dnase I-like fold. <ref name="IP5">PMID: 22381590</ref> | ||
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The N591K mutation also causes significant reduction in binding of Rab8a protein but the reason for this is different than in the case of F668V mutation. This AA is not part of any binding site but it seems to be important in the maintenance of the correct features of the ASH domain which are essential for the Rab8a binding. The effect of this mutation was studied in silico and the study showed that the mutation caused the ASH domain to alter its flexibility and overall fold. Although the most significant change was observed in the AAs that surrounded the N591K mutation, the substitution caused subsequent changes in most parts of the protein which brought about decreases of prevalence of hydrogen bonds between Rab8a and OCRL1 which led to a lower stability of their interaction.<ref name="com"/> | The N591K mutation also causes significant reduction in binding of Rab8a protein but the reason for this is different than in the case of F668V mutation. This AA is not part of any binding site but it seems to be important in the maintenance of the correct features of the ASH domain which are essential for the Rab8a binding. The effect of this mutation was studied in silico and the study showed that the mutation caused the ASH domain to alter its flexibility and overall fold. Although the most significant change was observed in the AAs that surrounded the N591K mutation, the substitution caused subsequent changes in most parts of the protein which brought about decreases of prevalence of hydrogen bonds between Rab8a and OCRL1 which led to a lower stability of their interaction.<ref name="com"/> | ||
==Inositol polyphosphate 5-phosphatase 3D structures== | |||
[[3D structures of inositol polyphosphate 5-phosphatase OCRL]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | |||