Sandbox Reserved 935

From Proteopedia

Revision as of 12:56, 15 May 2014

BRI^865-1196ADP (4OA2)

Introduction

Brassinosteroid insensitive 1 (BRI1) is a membrane receptor that senses brassinosteroides, which are polyhydroxylated steroid hormones ^[1]. Brassinosteroids control planth growth and development by activating BRI1 and starting a signaling pathway that leads to nuclear thanscription factors being activated. They do so by inducing rapid plant cell wall expansion and hyperpolarization ^[2]. The brassinosteroid induced association of BRI1 with the proton pump of P-type H+-ATPase also seems to be necessary for the activation of P-ATPase in the plasma membrane, though it is not currently known if it’s by serine/threonine phosphorylation or some other protein-protein interaction. BRI1 is thought to be a dual-specificity kinase and it has structural features reminiscent of both serine/threonine and tyrosine kinases ^[1].

In the cell, BRI1 cycles between the plasma membrane and endosomes ^[1]. When not activated, BRI1 is auto-inhibited by its own C-terminal tail as well as auto-phosphorylation of Thr872 and interaction with BRI1 kinase inhibitor protein BKI1 in the kinase domain. BKI1 also contains an N-terminal targeting motif for the plasma membrane. When the extracellular LRR domain gets activated by a brassinosteroid, it causes a reordering of 70 residues and creates a docking platform for the co-receptor SERK (somatic embryogenesis receptor kinase). The C-termini of BRI1 and SERK trans-phosphorylate each other, releasing the BKI1 from BRI1 and allowing BRI1 to phosphorylate immediate downstream signaling components (such as BRI1 substrate kinases, or BSKs).

In this article we will concentrate on the BRI1 kinase domain and its interaction with the nucleotides ATP/ADP.

Structure

BRI1 belongs to a group of membrane receptor kinases called LRR-RKs with an extracellular LRR ligand binding domain, a single membrane spanning helix and a cytoplasmic kinase domain ^[1]. The BRI1 nucleotide binding site is located between the N- and C-lobes of the protein.

The kinase domain adopts an active conformation with a salt-bridge between Lys911 and Glu927 ^[1]. There is also a hydrogen bond between Glu927 and Tyr956. This tyrosine residue is a gatekeeper determining the size of the nucleotide binding pocket. Comparison with other plant receptor-like kinases suggests this hydrogen bond interaction and salt-bridge are important for the activation, because they are holding the binding pocket in its active conformation.

Function

BRI1 is a dual-specificity kinase: it can both autophosphorylate on tyrosine residues in the kinase and juxtamembrabe domains (residues 814-865, part of which is not in this model) and also transphosphorylate tyrosine residues in other proteins ^[1]. The juxtamembrane domain is important for the kinase domain activity.

In this structure, the adenine and ribose parts of ADP are well ordered, whereas the diphosphate is more flexible ^[1]. There are hydrogen-bonding interactions of the adenine base and ribose with the BRI1 hinge region main chain atoms (E957, M959) and with two water molecules. When it was an ATP, the catalytic D1009 caused it to γ -phosphate to face outwards. BRI^865-1196 can efficiently hydrolyse ATP to ADP and to a lesser extent GTP to GDP.

Homologs

There are homologs for the kinase domain of BRI1 not only in plants but also in other eukaryotes ^[1]. Homologs in plants have similar domain structure in the whole protein, but in animals the other domains than kinase domain are different. The closest similarity to the kinase domain of BRI1 in Arabidopsis thaliana is interleukin-1 receptor-associated kinase 4 (IRAK4) in human and mouse. Similar kinase in Drosophila melanogaster is called Pelle-kinase.

References